Toxicology and Pharmacology of Aminoglycoside Antibiotics

  • T. Koeda
  • K. Umemura
  • M. Yokota
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 62)

Abstract

The major toxic effect of aminoglycosides is nephrotoxicity. In general, aminoglycosides are not metabolized in vivo, but are excreted by glomerular filtration. However, a portion can be reabsorbed via the proximal tubules and remain in the kidney, a process which may induce nephrotoxicity due to the damage of the tubules. Clinical pharmacologists have studied the detection of the early signs of nephrotoxicity and have searched for drugs which will alleviate nephrotoxicity.

Keywords

Toxicity Creatinine Heparin Streptomycin Acetylcholine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams HR (1973) Neuromuscular blocking effect of aminoglycoside antibiotic in nonhuman primate. J Am Vet Med Assoc 163:613–616PubMedGoogle Scholar
  2. Adams HR, Goodman FR, Weiss GB (1974) Alteration of contractile function and calcium ion movements in vascular smooth muscle by gentamicin and other aminoglycoside antibiotics. Antimicrob Agents Chemother 5:640–646PubMedGoogle Scholar
  3. Akiyoshi M (1979) Inner ear damage, its evaluation and safety administration of ototoxic aminoglycoside antibiotics, innermost row of the outer hair cells. Clin Bacteriol 6:353–361Google Scholar
  4. Akiyoshi M, Sato K (1967 a) Histopathological and enzyme histochemical studies on ototoxicity due to gentamicin and kanamycin in guinea pigs. Chemotherapy (Tokyo) 15:501–512Google Scholar
  5. Akiyoshi M, Sato K (1967 b) Histochemical demonstration of succinic dehydrogenase activity of the hair cells by means of intravital perfusion of the cochlea. Audiology Jpn 10:48–56Google Scholar
  6. Akiyoshi M, Sato K (1968) Functional, histopathological and histochemical studies on the ototoxicity in guinea pigs due to aminosidine. Chemotherapy (Tokyo) 16:134–138Google Scholar
  7. Akiyoshi M, Sato K (1969 a) Experimental study on the ototoxicity of aminodeoxykanamy- cin in guinea pig, pinna reflex and histopathologic findings. Chemotherapy (Tokyo) 17:1656–1663Google Scholar
  8. Akiyoshi M, Sato K (1969 b) Réévaluation of the pinna reflex test as screening for ototoxicity of antibiotics. Prog Antimicrob Anticancer Chemother. University of Tokyo Press, vol 1, pp 621–627Google Scholar
  9. Akiyoshi M, Sato K (1971) Ototoxicity of vistamycin. Audiology Jpn 14:189–201Google Scholar
  10. Akiyoshi M, Sato K (1973) Histochemical study of reduction potency of ubiquinone of hairn cells of the spiral organ in guinea pigs. Acta Histochem Cytochem 233–247Google Scholar
  11. Akiyoshi M, Sato K, Sugahiro K, Shoji T (1968) Functional, histochemical and istopathological studies on ototoxicity of enduracidin in guinea pigs. Chemotherapy (Tokyo) 16:511–520Google Scholar
  12. Akiyoshi M, Sato K, Tamura H (1972) Ototoxicity of liviodomycin. Audiology Jpn 15:220–223Google Scholar
  13. Akiyoshi M, Sato K, Nakada H, Tojima T (1974 a) Audiometrical and histopathological evaluation of ototoxicity of 3,4-dideoxykanamycin B (DKB), a new semisynthetic aminoglycoside antibiotic in guinea pigs. Jpn J Antibiot 27:15–26PubMedGoogle Scholar
  14. Akiyoshi M, Sato K, Shoji T, Sugahiro K, Tajima T, Koeda T, Odaki M, Yokata M (1974 b) Ototoxic effect of 3’,4’-dideoxykanamycin B on the inner ear in the intrauterine guinea pigs. Jpn J Antibiot 27:735–745PubMedGoogle Scholar
  15. Akiyoshi M, Sato K, Nakada H, Nara T, Tajima T, Sasaki K, Ogawa M (1975 a) Ototoxicity of tobramycin in guinea pigs. Chemotherapy (Tokyo) 23:1522–1543Google Scholar
  16. Akiyoshi M, Sato K, Nakada H, Tajima T, Suzuki K, Kishimoto K (1975 b) Evaluation of ototoxicity of amikacin (BB-K8) by animal test. Jpn J Antibiot 28:288–304PubMedGoogle Scholar
  17. Akiyoshi M, Iwazawa T, Yano S, Shoji T, Tajima T, Hara T, Shimizu M (1977) Animal test for evaluation of ototoxicity and safety of KW-1062. Chemotherapy (Tokyo) 25:1892–1914Google Scholar
  18. Albiero L, Ongini E, Parravicini L (1978) The neuromuscular blocking activity of a new aminoglycoside antibiotic netilmicin sulphate. Eur J Pharmacol 50:1–7PubMedGoogle Scholar
  19. Alleva FR, Balzas T (1978) Toxic effects of potential administration of streptomycin sulfate to rats. Toxicol Appl Pharmacol 45:855–859PubMedGoogle Scholar
  20. Anhalt JP (1977) Assay of gentamicin in serum by highpressure liquid chromatography. Antimicrob Agents Chemother 11:651–655PubMedGoogle Scholar
  21. Aratani H, Yamanaka Y, Onishi R, Kono S, Hashimoto T, Hirozane T (1968) Pharmacological studies on amidosidine. Chemotherapy (Tokyo) 6:114–120Google Scholar
  22. Asakuma S, Shida S, Suzuki M, Abe N (1975) Experimental study on the mutual relation between endocochlea DC potential and cochlear microphonics. Audiology Jpn 18:246–254Google Scholar
  23. Barza M, Brown RB, Shen D, Gibaldi M, Weinstein L (1974) Predictability of blood levels of gentamicin in man. Clin Res 22:687AGoogle Scholar
  24. Boger WP, Gavin JJ (1958–1959) Kanamycin: its cerebrospinal fluid diffusion, renal clearance and comparison with streptomycin. Antibiot Annu 676–677Google Scholar
  25. Brazil OV, Corrado AP (1957) The curariform action of streptomycin. J Pharmacol Exp Ther 120:452–459PubMedGoogle Scholar
  26. Brazil OV, Prado-Franceschi J (1969) The neuromuscular blocking action of gentamicin. Arch Int Pharmacodyn Ther 179:65–76Google Scholar
  27. Broughall JM, Reeves DS (1975 a) Properties of the gentamicin acetyltransferase enzyme and application to the assay of aminoglycoside antibiotics. Antimicrob Agents Chemother 8:222–223PubMedGoogle Scholar
  28. Broughall JM, Reeves DS (1975 b) The acetyltransferase enzyme method for the assay of serum gentamicin concentrations and a comparison with other methods. J Clin Pathol 28:140–145PubMedGoogle Scholar
  29. Broughton A, Strong JE, Pickering LK, Bodey GP (1976 a) Radioimmunoassay of io-dinated tobramycin. Antimicrob Agents Chemother 10:652–656PubMedGoogle Scholar
  30. Broughton A, Strong JE, Bodey GP (1976 b) Radioimmunoassay of sisomicin. Antimicrob Agents Chemother 9:247–250PubMedGoogle Scholar
  31. Brown RD, Feldman AM (1978) Pharmacology of hearing and ototoxicity. Annu Rev Pharmacol Toxicol 18:233–252PubMedGoogle Scholar
  32. Barza M, Brown RB, Shen D, Gibaldi M, Weinstein L (1975) Predictability of blood levels of gentamicin in man. J Infect Dis 132:165–174PubMedGoogle Scholar
  33. Benzi G, Arrigoni E, Pancer P, Berte F (1972) Action on gentamicin, aminosidine, and am-picillin on uterine tone and motility. Jpn J Pharmacol 22:571–576PubMedGoogle Scholar
  34. Berg K (1951) The toxic effect of streptomycin on the vestibular and cochlear apparatus.Acta Otolaryngo [Suppl] (Stockh) 97:1–47Google Scholar
  35. Bergeron MG, Trottier S (1979) Influence of single or multiple doses of gentamicin and netilmicin on their cortical, medullary and papillary distribution. Antimicrob Agents Chemother 15:635–641PubMedGoogle Scholar
  36. Berggärd I, Beam AG (1968) Isolation and properties of low molecular weight ß2-microglo- bulin occurring in human biological fluids. J Biol Chem 243:4095–4103PubMedGoogle Scholar
  37. Bernard B, Abate M, Thielen PF, Attar H, Ballard CA, Wehrle PF (1977) Maternal-fetal pharmacological activity of amikacin. J Infect Dis 135:925–932PubMedGoogle Scholar
  38. Bodey GP, Valdivieso M, Feld R, Rodriguez V (1974) Pharmacology of amikacin in humans. Antimicrob Agents Chemother 5:508–512PubMedGoogle Scholar
  39. Brummett RE (1972) A comparative study of the ototoxicity of tobramycin and gentamicin. Arch Otolaryngol 96:505–512PubMedGoogle Scholar
  40. Brummett RE, Traynor J, Brown R, Himes D (1975) Cochlear damage resulting from kanamycin and furosomide. Acta Otolaryngol (Stockh) 80:86–92Google Scholar
  41. Cabana BE, Taggart JG (1973) Comparative pharmacokinetics of BB-K8 and kanamycinin dogs and humans. Antimicrob Agents Chemother 3:478–483PubMedGoogle Scholar
  42. Chauvin JM, Rudhardt M, Bluauchard P, Gaillard R, Fabre J (1978) Le compartment de la gentamicine dans le parenckyme renal. Schweiz Med Wochenschr 108:1020–1025PubMedGoogle Scholar
  43. Child KJ, Davis B, Sharpe HM, Tomich EG (1956–1957) Toxicologic studies on the sulfate and pantothenates of streptomycin and dihydrostreptomycin. Antibiot Annu 574–580Google Scholar
  44. Chiu PJS, Long JF (1978) Effects of hydration on gentamicin excretion and renal accumulation in furosemide-treated rats. Antimicrob Agents Chemother 14:214–217PubMedGoogle Scholar
  45. Chiu PJS, Brown A, Miller G, Long JF (1976) Renal extraction of gentamicin in anesthetized dogs. Antimicrob Agents Chemother 10:277–282PubMedGoogle Scholar
  46. Chiu PJS, Miller GH, Brown AD, Long JF, Waitz JA (1977) Renal pharmacology of netilimicin. Antimicrob Agents Chemother 11:821–825PubMedGoogle Scholar
  47. Collier VU, Mitch WE, Lietman PS (1978) Tubular uptake of gentamicin by the intact kidney. Clin Res 26:288AGoogle Scholar
  48. Crawford LM, Bowen JM (1971) Calcium binding as a property of kanamycin. Am J Vet Res 32:357–359PubMedGoogle Scholar
  49. Danish M, Schultz R, Jusco J (1974) Pharmacokinetics of gentamicin and kanamycin during hemodialysis. Antimicrob Agents Chemother 6:841–847PubMedGoogle Scholar
  50. Daschner F, Reiss E, Engert J (1977) Distribution of amikacin in serum, muscle and fat in children after a single intramuscular injection. Antimicrob Agents Chemother 11:1081- 1083PubMedGoogle Scholar
  51. Davis WW, Stout TR (1971) Disk plate method of microbiological antibiotic assay II, novel procedure offering improved accuracy. Appl Microbiol 22:666–670PubMedGoogle Scholar
  52. Dellinger P, Murphy T, Barza M, Pinn V, Weinstein L (1976) Effect of cephalothin on renal cortical concentration of gentamicin in rats. Antimicrob Agents Chemother 9:587–588PubMedGoogle Scholar
  53. Dettli L (1971) Multiple dose kinetics and drug dosage in patients with kidney disease. Acta Pharmacol Toxicol 29:211Google Scholar
  54. Edwards CQ, Smith CR, Baugman KL, Rogers JF, Lietman PS (1976) Concentration of gentamicin and amikacin in human kidneys. Antimicrob Agents Chemother 9:925–927PubMedGoogle Scholar
  55. Engström H, Kohonen A (1965) Cochlear damage from ototoxic antibiotics. Acta Otolaryngol (Stockh) 59:171–178Google Scholar
  56. Ervin FR, Bullock WE Jr, Nuttal CE (1976) Inactivation of gentamicin by penicillins in patients with renal failure. Antimicrob Agents Chemother 9:1004–1011PubMedGoogle Scholar
  57. Ezer J, Mahon WA, Inaba T (1976) Tissue distribution and selective kidney uptake of triti-ated aminoglycosides in the rats. Pharmacologist 18:206Google Scholar
  58. Fujisawa K, Hoshiya T, Kawaguchi H (1974) Aminoglycoside antibiotics. VII. Acute toxicity of aminoglycoside antibiotics. J Antibiot (Tokyo) 27:677–681Google Scholar
  59. Fujita M, Fukushima K, Abe M, Tomono N, Umemura K (1973) Experimental studies on absorption, excretion, distribution, and metabolism of 3’4’-dideoxy kanamycin B. II. Absorption, excretion, and distribution in rabbits and dogs. Jpn J Antibiot 26:55–60Google Scholar
  60. Fukushima K, Fujita M (1970) Teratological study of vistamicin. Clin Rep 4:52–61Google Scholar
  61. Furuno K, Andoh K, Suzuki S (1976 a) Effect of D-glucarates on basic antibiotic-induced renal damage in rats. J Antibiot (Tokyo) 29:187–194Google Scholar
  62. Furuno K, Matsubara S, Andoh K, Suzuki S (1976 b) Preventive effect of D-glucarate against renal damage induced by kanamycin. J Antibiot (Tokyo) 29:950–953Google Scholar
  63. Furuno K, Suzuki S, Hirata K (1977) Influence of dehydration and D-glucarate on distribution and excretion of kanamycin in rats. Jpn J Pharmacol 27:371–378PubMedGoogle Scholar
  64. Garrod LP, Gruenwaldt G, Marget W, Wellta H (1979) New aspects of aminoglycoside therapy, sisomicin. Infection 7:294–300Google Scholar
  65. Gergis SD, Dretchen KL, Sokoll MD, Long JP (1971) The effects of neuromuscular blocking agents on acetylcholine release. Proc Soc Exp Biol Med 38:693–695Google Scholar
  66. Goodman FR (1978) Distribution of gentamicin in vascular smooth muscle. Pharmacology 16:17–25PubMedGoogle Scholar
  67. Gordon RC, Regamey C, Kirby WMM (1972) Serum protein binding of the aminoglycoside antibiotics. Antimicrob Agents Chemother 2:214–216PubMedGoogle Scholar
  68. Haas MJ, Davis J (1973) Enzymatic acetylation as a means of determining serum aminoglycoside concentrations. Antimicrob Agents Chemother 4:497–499PubMedGoogle Scholar
  69. Hara T, Nishikawa S, Miyazaki H, Ohguro Y (1980) Studies on the safety of KW-1062 (Fifth report), a comparative study on the renal toxicity of KW-1062 and gentamicin in rats by light and electron microscopies. Jpn J Antibiot 33:1–9PubMedGoogle Scholar
  70. Harada Y, Mori S, Teshima K, Ino M, Nakatani Y, Hirota K, Ishikawa M, Toyota H, Kawase M, Matsumura S, Kimoto S, Uno O, Nakao T (1975) Subacute toxicologic studies with tobramycin and its recovery studies in beagle dogs. Chemotherapy 23:1494–1521Google Scholar
  71. Hasegawa Y, Yoshida T, Kozen T, Yamagata H, Sakaguchi I, Okamoto A, Ohara T, Kozen T (1975) Teratological studies on tobramycin in mice and rats. Chemotherapy 23:1544–1553Google Scholar
  72. Hashimoto T, Ichikawa S, Kojima T (1977) The general pharmacological action of KW-1062, a new aminoglycoside antibiotics. Jpn J Antibiot 30:362–385PubMedGoogle Scholar
  73. Hawkins JE Jr (1959) The ototoxicity of kanamycin. Ann Otol Rhinol Laryngol 68:698–715PubMedGoogle Scholar
  74. Hawkins JE Jr, Arbor A (1976) Drug ototoxicity. In: Kiedel WD, Neff WD (eds) Auditory system. Clinical and special topics. Springer, Berlin Heidelberg New York (Handbook of sensory physiology, vol 5/3, pp 707–748)Google Scholar
  75. Hawkins JE Jr, Engstrom H (1964) Effects of kanamycin on cochlear cytoarchitecture. Acta Otol Laryngol [Suppl] (Stockh) 188:100–107Google Scholar
  76. Hawkins JE Jr, Wolcott H, O’Skanny WJ (1956–1957) Ototoxic effects of streptomycin and dihydrostreptomycin pantothenates in the cat. Antibiot Annu 554–563Google Scholar
  77. Hawkins S (1958) Pharmacology of neomycin. In: Waksman SA (ed) Neomycin, its nature and practical application. Williams &Wilkins, Baltimore, pp 130–146Google Scholar
  78. Hirokawa N, Haruyama A, Oike S, Naruse T (1979) Clinical evaluation of N-acetyl- glucosaminidase activity in 60 patients treated with aminoglycosides. Curr Chemother Infect Dis 1:626–627Google Scholar
  79. Hoecker JL (1978) Clinical pharmacology of tobramycin in children. J Infect Dis 137:592–596PubMedGoogle Scholar
  80. Hoeffler D, Koeppe P, Demers HG (1976) Pharmacokinetics of amikacin for treatment of urinary tract infections in patients with reduced renal function. J Infect Dis 134:S369–373Google Scholar
  81. Holmes RK, Sanford JP (1974) Enzymatic assay for gentamicin and related aminoglycoside antibiotics. J Infect Dis 129:519–527PubMedGoogle Scholar
  82. Hori K, Kawamoto K (1972) The experimental study of the side effect of lividomycin on the inner ear. Audiology Jpn 15:212–219Google Scholar
  83. Hsu CH, Kurtz TW, Easterling RE, Weller JM (1974) Potentiation of gentamicin nephrotoxicity by metabolic acidosis (38212). Proceedings of the Society for Experimental Biology and Medicine 146:894–897PubMedGoogle Scholar
  84. Hsu CH, Kurtz TW, Weller JM (1977) In vitro uptake of gentamicin by rat renal cortical tissue. Antimicrob Agents Chemother 13:192–194Google Scholar
  85. Ichikawa T, Nakano I, Hirokawa I, Okada K, Abe M, Umemura K (1973) Experimental studies on absorption, excretion, distribution, and metabolism of 3’-4’-dideoxykanamy- cin B. III. Pharmacokinetic analysis in man. Jpn J Antibiot 26:262–266PubMedGoogle Scholar
  86. Ikeda C, Tachibana A, Yano K (1979) Absorption, distribution, metabolism, and excretion of sisomicin in mice, rats, and dogs. Jpn J Antibiot 32:312–322PubMedGoogle Scholar
  87. Inoue S (1972) Recent progress in the aminosugar antibiotics. Sci Rep Meiji Seika Kaisha 12:1–55Google Scholar
  88. Israel KS, Welles JS, Black HR (1976) Aspects of the pharmacology and toxicology of tobramycin in animals and humans. J Infect Dis [Suppl] 134:97–103Google Scholar
  89. Ito Y (1962 a) Chemistry of basic oligosaccharide antibiotics (1). Pharm Month 34:1–35Google Scholar
  90. Ito Y (1962 b) Chemistra of basic oligosaccharide antibiotics (2). Pharm Month 34:74–99Google Scholar
  91. Ito Y (1963) Recent advances in the chemistry of basic oligosaccharide antibiotics. Pharm Month 34:293–315Google Scholar
  92. Jackson GG, Finland M (1969) International symposium on gentamicin, a new aminoglycoside antibiotic. J Infect Dis 119:4–5Google Scholar
  93. Jaffe G, Meyers BR, Hirschman SZ (1974) Pharmacokinetics of tobramycin in patients with stable renal impairment, patients, undergoing peritoneal dialysis, and patients on chronic hemodialysis. Antimicrob Agents Chemother 5:611–616PubMedGoogle Scholar
  94. Jerauld R, Silverblatt FJ (1978) Effect of N-methylnicotinamide on the renal accumulation and reabsorption of gentamicin in rats. Antimicrob Agents Chemother 13:893–894PubMedGoogle Scholar
  95. Kajimoto Y, Kuramoto M (1967) Toxicity of gentamicin. Chemotherapy (Tokyo) 15:490–496Google Scholar
  96. Kaneko Y, Nakagawa T, Tanaka K (1970) Reissner’s membrane after kanamycin administration. Arch Otolaryngol 92:457–462PubMedGoogle Scholar
  97. Kanzaki J (1966) The Preyer’s reflex of the guinea pig as the hearing index. Audiology Jpn 60:940–948Google Scholar
  98. Keller H, Krupe W, Sous H, Muckter H (1955) The reduction of the toxicity of basic strep- tomyces antibiotics. I. Streptomycin and dihydrostreptomycin. Arzneim Forsch 5:170–176Google Scholar
  99. Kellerhals B (1979) Perilymph production and cochlear blood flow. Acta Otolaryngol (Stockh) 187:370–374Google Scholar
  100. Kendall MJ, Wise R, Andrews JM, Bedford KA (1978) A pharmacological study of VK-18892 and amikacin. Antimicrob Agents Chemother 4:459–463Google Scholar
  101. Kirby WMM, Clarke JT, Libke RD, Regamey C (1976) Clinical pharmacology of amikacin and kanamycin. J Infect Dis 134:S312–315PubMedGoogle Scholar
  102. Kluwe WM, Hook JB (1978) Functional nephrotoxicity of gentamicin in the rat. Toxicol Appl Pharmacol 45:163–175PubMedGoogle Scholar
  103. Koeda T, Moriguchi M (1973) Teratological studies of 3’,4’-dideoxykanamycin B in rats and mice. Jpn J Antibiot 26:40–48Google Scholar
  104. Koeda T, Odaki M, Niizato T, Watanabe H (1970 a) Toxicological studies of vistamycin. Clin Rep 4:14–37Google Scholar
  105. Koeda T, Shibata U, Nakazawa T, Asaoka H, Yamagami K (1970 b) Pharmacological studies on vistamycin. Clin Rep 4:39–51Google Scholar
  106. Koeda T, Odaki M, Hisamatsu T, Sasaki H, Yokota M, Niizato T, Uchida S (1973 a) Studies on subacute toxicity of 3’,4’-dideoxykanamycin B (DKB). Jpn J Antibiot 26:228–246PubMedGoogle Scholar
  107. Koeda T, Odaki M, Hisamatsu T, Sasaki H, Yokota M, Niizato T, Uchida S (1973 b) Studies on chronic toxicity of 3’,4’-dideoxykanamycin B. Jpn J Antibiot 26:247–261PubMedGoogle Scholar
  108. Koeda T, Shibata U, Asaoka H, Kabata Y, Yamaki Y (1973 c) Pharmacological studies on 3’,4’-dideoxykanamycin B (DKB). Jpn J Antibiot 26:28–39PubMedGoogle Scholar
  109. Komiya I, Hayasaka Y, Murata S, Komai T, Umemura K (1973) Experimental studies on absorption, excretion, distribution, and metabolism of 3’,4’-dideoxykanamycin B. I. Absorption, excretion, distribution, and metabolism in rats. Jpn J Antibiot 26:49–54PubMedGoogle Scholar
  110. Komiya I, Murata S, Umemura K, Tomono N, Kikai S, Fujita M (1981 a) Pharmacokinetics of dibekacin in rabbits and dogs. J Pharm Dyn, vol 4, pp 362–373Google Scholar
  111. Komiya I, Murata S, Umemura K, Tomono N, Kikai S, Fujita M (1981 b) Acute toxicity and pharmacokinetics of dibekacin in mice. J Pharm Dyn, vol 4, pp 356–361Google Scholar
  112. Kornguth ML, Kunin CM (1977) Distribution of gentamicin and amikacin in rabbit tissues. Antimicrob Agents Chemother 11:974–977PubMedGoogle Scholar
  113. Kuhar MJ, Mak LL, Lietman P (1979) Autoradiographic localization of [3H] gentamicin in the proximal renal tubules of mice. Antimicrob Agents Chemother 15:131–133PubMedGoogle Scholar
  114. Kuramoto M, Okubo T, Lee S, Ishimura Y, Morimoto J (1975) Toxicological studies of tobramycin in mice and rats. Chemotherapy (Tokyo) 23:1470–1493Google Scholar
  115. Lamb JW, Mann JM, Simmons RJ (1972) Factors influencing the microbiological assay of tobramycin. Antimicrob Agents Chemother 1:323–328PubMedGoogle Scholar
  116. Lange G (1975) Das Verhalten der Labyrinth-Funktionen des Affen (Macacus rhesus) unter Streptomycin-Belastung. Arch Otorhinolaryngol 211:35–41PubMedGoogle Scholar
  117. Lawson DH (1972) Effects of furosemide on antibiotic-induced renal damage in rats. J Infect Dis 126:593–600PubMedGoogle Scholar
  118. Letourneau Saseb L, Lapierre L, Daigneault R, Homme MP, St Lous G, Sirois G (1977) Gentamicin pharmacokinetics during hemodialysis in patients suffering from chronic renal failure. Int J Clin Pharmacol Biopharm 15:116–120Google Scholar
  119. Levy J, Klastersky J (1975) Correlation of serum creatinine concentration and amikacin half-life. J Clin Pharmacol 15:705–707PubMedGoogle Scholar
  120. Lewis JE, Nelson JS, Elder HA (1972) Radioimmunoassay of an antibiotic gentamicin. Nature New Biol 239:214–215PubMedGoogle Scholar
  121. Lewis JE, Nelson JC, Elder HA (1975) Amikacin; a rapid and sensitive radioimmunoassay. Antimicrob Agents Chemother 7:42–45PubMedGoogle Scholar
  122. Lindsen JR, Proctor LR, Work WP (1960) Histopathologic inner ear changes in deafness due to neomycin in a human. Laryngoscope 70:382–392Google Scholar
  123. Lockwood WR, Bower JD (1973) Tobramycin and gentamicin concentrations in the serum of normal and anephric patients. Antimicrob Agents Chemother 3:125–129PubMedGoogle Scholar
  124. Luft FC, Kleit SA (1974) Renal parenchymal accumulation of aminoglycoside antibiotics in rats. J Infect Dis 130:656–659PubMedGoogle Scholar
  125. Luft FC, Walker PD, Yum MN, Kleit SA (1975) Gentamicin concentration in human kidney cortex. Clin Res 23:477AGoogle Scholar
  126. Lund ME, Blazevic DJ, Matsen JM (1973) Rapid gentamicin bioassay using a multiple-anti- biotic-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 4:569–573PubMedGoogle Scholar
  127. Lurie MH, Rahway NJ (1956) The ototoxicity of dihydrostreptomycin and neomycin in the cat. Ann Otol Rhinol Laryngol 62:1128–1148Google Scholar
  128. Lutz MD (1978) Characteristic of gentamicin accumulation by proximal straight renal tubules in vitro. Clin Res 26:140AGoogle Scholar
  129. Madhavan T, Yaremchuk K, Levin N, Pohlod D, Burch K, Fisher E, Cox F, Quinn EL (1976) Effect of renal failure and dialysis on the serum concentration of the aminoglycoside, mikacin. Antimicrob Agents Chemother 10:464–466PubMedGoogle Scholar
  130. Maitra SK, Yoshikawa TT, Steyn CM, Guze LB, Schotz MC (1978) Amikacin assay in serum by high-performance liquid chromatography. Antimicrob Agents Chemother 14:880–885PubMedGoogle Scholar
  131. Malacoff RE, Finkelstein FO, Andriole VT (1975) Effect of peritoneal dialysis on serum levels of tobramycin and clindamycin. Antimicrob Agents Chemother 8:574–580PubMedGoogle Scholar
  132. Matsuzaki M, Nakamura K, Akutsu S, Sekino M, Hirata A, Asano M, Kishimoto K, Fukushima M (1975 a) Studies on the toxicity of amikacin (BB-K8), I. Acute toxicity and subacute toxicity in rats. Jpn J Antibiot 28:415–433PubMedGoogle Scholar
  133. Matsuzaki M, Nakamura Y, Yoshida A, Sekine M, Iisue K, Asano M, Onodera K, Watanabe K (1975 b) Studies on the toxicity of amikacin (BB-K8). II. Chronic toxicity in rats. Jpn J Antibiot 28:434–457Google Scholar
  134. Matsuzaki M, Akutsu S, Yoshida A, Onodera A, Sekine M, Tsuchida M, Asano M (1975 c) Studies on the toxicity of amikacin (BB-K8). III. Subacute toxicity of amikacin (BB-K8) in dogs. Jpn J Antibiot 28:458–484PubMedGoogle Scholar
  135. Matsuzaki M, Yoshida A, Akutsu S, Nakamura K, Sekino M, Okuyama D, Asano M (1975 d) Studies on the toxicity of amikacin (BB-K8). IV. Chronic toxocity in dogs. Jpn J Antibiot 28:485–523PubMedGoogle Scholar
  136. Matsuzaki M, Onodera K, Okazaki I, Nakajima A, Akima T, Koshino M, Kishimoto K (1975 e) Pharmacological studies of amikacin (BB-K8). Jpn J Antibiot 28:385–400PubMedGoogle Scholar
  137. Mays DL, VanApeldoorn RJ, Lauback RG (1976) High-performance liquid chromatographic determination of kanamycin. J Chromatogr 120:93–102PubMedGoogle Scholar
  138. McHenry MC, Wagner JG, Hall PM, Vidt DG, Gavan TL (1976 a) Amikacin in renal failure. Clin Pharmacol Ther 19:112aGoogle Scholar
  139. McHenry MC, Wagner JG, Hall PM, Vidt DG, Gavan TL (1976 b) Pharmacokinetics of amikacin in patients with impaired renal function. J Infect Dis 134:S343–354PubMedGoogle Scholar
  140. Meyers BR, Hirschman SZ, Warmser G, Siegel D (1977) Pharmacokinetic study of netilmicin. Antimicrob Agents Chemother 12:122–123PubMedGoogle Scholar
  141. Mirhij NJ, Roberts RJ, Myers MG (1978) Effect of hypoxemia upon aminoglycosides serum pharmacokinetics in animals. Antimicrob Agents Chemother 14:344–347PubMedGoogle Scholar
  142. Mitchell CJ, Bullock S, Ross BD (1977) Renal handling of gentamicin and other antibiotics by the isolated rat kidney. Antimicrob Agents Chemother 3:593–600Google Scholar
  143. Molgó J, Lameignan M, Uchiyama T, Lechat P (1979) Inhibitory effect of kanamycin on evoked transmitter release. Reversal by 3’,4’-diaminopyridine. Eur J Pharmacol 57:93–97PubMedGoogle Scholar
  144. Momose S (1969) A new approach to the pathogenesis of acute tubular necrosis: with special reference to tubular damages occurred from coincidental administration of aminoglycoside antibiotics and sodium alginate. Jpn J Urol 60:823–833Google Scholar
  145. Mondorf AW, Breider J, Hendus J, Scherberich JE, Mackenrodt G, Shah PM, Stille W, Schoeppe W (1978) Effect of aminoglycosides on proximal tubular membranes of the human kidney. Eur J Clin Pharmacol 13:133–142PubMedGoogle Scholar
  146. Mootz W, Schondorf J, Werner G (1972) Elektronenmikroskopische Untersuchungen am Plexus cochlearis nach Kanamycinintoxikation. Acta Otolaryngol (Stockh) 73:38–43Google Scholar
  147. Mori H, Koga T, Kawahara T, Tamura H, Nakamura T (1972 a) The safety test of livid- omycin (1). Acute, subacute and chronic toxicity test of lividomycin. Pharmacometrics 6:787–812Google Scholar
  148. Mori H, Kakishita T, Katoh Y (1972 b) The safety test of lividomycin (2). Effect of lividomycin on development of fetuses and newborns’ mouse. Pharmacomedia 6:813–820Google Scholar
  149. Mori H, Saitoh N, Katoh Y (1973) The safety test of liviodomycin (5). Effect of lividomycin on development of fetuses and newborn of rabbits. Pharmacomedia 7:1241–1250Google Scholar
  150. Moriyama S (1959) Studies on streptomycin deafness in its early stage. Jpn Otolaryngol 62:107–118Google Scholar
  151. Murata S, Kadosawa H, Shomura T, Umemura K (1971) Distribution, metabolism and excretion of ribostamycin. Yakuzaigaku 3:1–7Google Scholar
  152. Nakai Y, Yamamoto K, Iwamoto T (1972) Electromicroscopic study of kanendomycin and vistamycin ototoxicity. Audiology Jpn 15:202–210Google Scholar
  153. Nakai Y, Yamamoto K, Zushi K, Fujimoto A (1974) The influence of amikacin (BB-K8) upon the cochlea. An electron microscopical study. Jpn J Antibiot 27:212–217PubMedGoogle Scholar
  154. Nakai Y, Fujimoto A, Yamamoto K (1975) Combined effect of aminoglycoside antibiotics and potent diuretics on the cochlea. Audiology Jpn 18:290–298Google Scholar
  155. Nakazawa S, Satoh H, Watanabe O, Sadaoka K, Fujii N, Abe M, Umemura K (1973) Experimental studies on absorption, excretion, distribution, and metabolism of 3’,4’- dideoxykanamycin B. IV. Pharmacokinetic analysis in pediatric field. Jpn J Antibiot 26:454–458PubMedGoogle Scholar
  156. Nieminen L, Kasaun A, Kangas L, Sairio E, Anttila M (1978) Renal accumulation of amikacin, tobramycin, and gentamicin in the rat. Experientia 34:1335–1336PubMedGoogle Scholar
  157. Niizato T, Koeda T, Tsuruoka T, Inoue S, Niida T (1976) Protective effects of D-glucaro- δ-lactam against aminoglycoside-induced nephrotoxicity in rats. J Antibiot (Tokyo) 29:833–840Google Scholar
  158. Noone P, Pasaons TMC, Pattison JR, Slack RCB, Garfield-Davis D, Hughes K (1974) Experience in monitoring gentamicin therapy during treatment of serious gram-negative sepsis. Br Med J 1:477–481PubMedGoogle Scholar
  159. Nurazyan AG (1976) Absorption, distribution, and retention of neomycin in gravid rabbits and fetus. Antibiotiki 21:625–630Google Scholar
  160. Ogawa A (1975) The effects of ototoxic antibiotics on the sensory epithelia of the inner ear; a functional and histochemical study. Audiology Jpn 18:1–19Google Scholar
  161. Ohtani I, Ohtsuki K, Omata T, Ouchi J, Saito T (1977) Potentiation of cochlear and renal damage resulting from furosemide and aminoglycoside antibiotics. Chemotherapy (Tokyo) 25:2348–2360Google Scholar
  162. Ohtani I, Ohtsuki K, Omata T, Ouchi J (1978 a) Interaction of bumetanide and kanamycin. Audiology Jpn 81:554–561Google Scholar
  163. Ohtani I, Ohtsuki K, Omata T, Ouchi J, Saito T (1978 b) Potentiation and its mechanism of cochlear damage resulting from furosemide and aminoglycoside antibiotics. ORL 40:53–63PubMedGoogle Scholar
  164. Ohtani I, Ohtsuki K, Aikawa T, Ouchi J, Nakayoshi T (1979) A comparative study on the ototoxicity of dibekacin and tobramycin administered by intravenous infusion. Jpn J Antibiot 32:990–997PubMedGoogle Scholar
  165. Ohyama S, Yoshimura M (1975) The role and behavior of the endocochlear potential in the inner ear. Audiology Jpn 18:255–260Google Scholar
  166. Oksenhendler G, Leroy A, Humbert G, Fillastre JP, Winkler C (1977) Pharmacocinetique des nouveaux antibiotiques du groupe des aminosides: tobramycine, lividomycine, ami- kacine, sisomycine chez le sujet a function renale normale et chez l’insuffisant renal regies de posologie. Anesth Analg (Paris) 34:93–110Google Scholar
  167. Oshita K (1959) Pharmacological studies on kanamycin. Med J Hiroshima Univ 7:1029- 1062Google Scholar
  168. Otori H (1967) Influence of gentamicin on the fetuses of Wistar rats and KR-JCK mice. Chemotherapy (Tokyo) 15:497–500Google Scholar
  169. Paradelis AG, Triantaphyllidis C, Fidani V, Logaras G (1974) The action of the aminogly- cosidic antibiotic gentamicin on isolated rat diaphragm. Arzneim Forsch (Drug Res) 24:1774–1779Google Scholar
  170. Paradelis AG, Triantaphyllidis C, Markomichelakis JM, Logaras G (1977) The neuromuscular blocking activity of aminodeoxykanamycin as compared with that of other aminoglycoside antibiotics. Arzneim Forsch 27:141–143Google Scholar
  171. Parker FL, James WL (1978) The effect of various topical antibiotic and antibacterial agents on the middle and inner ear of the guinea pig. J Pharm Pharmacol 30:236–239PubMedGoogle Scholar
  172. Pechére JC, Dugal R (1976) Pharmacokinetics of intravenously administered tobramycin in normal volunteers and renal impaired and hemodialyzed patients. J Infect Dis 134:S118–124PubMedGoogle Scholar
  173. Pechére JC, Roy B, Dugal R (1976 a) Distribution and elimination kinetics of intravenously and intramuscularly administered tobramycin in man. Int J Clin Pharmacol Biopharm 14:313–318PubMedGoogle Scholar
  174. Pechére JC, Pechere M-M, Dugal R (1976 b) Clinical pharmacokinetics of sisomicin: dosage schedules in renal impaired patients. Antimicrob Agents Chemother 9:761–765PubMedGoogle Scholar
  175. Pechére JC, Dugal R, Pechere MM (1978 a) Kinetics of netilmicin in man. Clin Pharmacol Ther 23:677–684PubMedGoogle Scholar
  176. Pechére JC, Dugal R, Pechere MM (1978 b) Pharmacokinetics of netilmicin in renal insufficiency and hemodialysis. Clin Pharmacokinet 3:395–506PubMedGoogle Scholar
  177. Penang GW, Jackson GG, Chion WK (1977) High-pressure liquid chromatographic assay of netilmicin in plasma. Antimicrob Agents Chemother 12:707–709Google Scholar
  178. Pijck J, Hallynck T, Soep H, Baert L, Daneels R, Baelaert J (1976) Pharmacokinetics of amikacin in patients with renal insufficiency: relation of half-life and creatinine clearance. J Infect Dis 134:5331–5341Google Scholar
  179. Raab WP, Windisch J (1973) Antagonism of neomycin by heparin. Arzneim Forsch 23:1326–1328Google Scholar
  180. Ramirez-Ronda CH, Holms RK, Sanford JP (1975) Effect of divalent cations on binding of aminoglycoside antibiotics to human serum proteins and to bacteria. Antimicrob Agents Chemother 7:239–245PubMedGoogle Scholar
  181. Rauws AG, VanKlingeren B (1978) Estimation of antibiotic levels in interstitial fluid from whole tissue levels. Scand J Infect Dis [Suppl] 14:186–188Google Scholar
  182. Regamey C, Schaberg D, Kirby WMM (1972) Inhibitory effect of heparin on gentamicin concentrations in blood. Antimicrob Agents Chemother 1:329–332PubMedGoogle Scholar
  183. Regeur L, Golding H, Jensen H, Kampman JP (1977) Pharmacokinetics of amikacin during hemodialysis and peritoneal dialysis. Antimicrob Agents Chemother 11:214–218PubMedGoogle Scholar
  184. Reiffensten JC, Holmes SW, Hottendorf GH, Bierwagen MF (1973) Ototoxicity studies with BB-K8, a new semisynthetic aminoglycoside antibiotic. J Antibiot (Tokyo) 26:94–100Google Scholar
  185. Revert C, Fillastre JP, Godin M, Leroy A (1978) Pharmacocinetique de la gentamicine; administration intramusculare de trois doses differentes chez des sujets ayant une fonction renale normale. Therapie 33:713–722PubMedGoogle Scholar
  186. Ritschel WA, Banarer M, Lau Chang EF (1977) Computer-calculated kanamycin dosage regimen and monitoring. Int J Clin Pharmacol Biopharm 15:121–125PubMedGoogle Scholar
  187. Robinson GC, Cambon KG (1964) Hearing loss in infants of tuberculous methods treated with streptomycin during pregnancy. N Engl J Med 271(18):949–951PubMedGoogle Scholar
  188. Roth S, Naber K, Scheer M, Gruenwaldt G, Lange H (1976) Pharmacokinetics of sisomicin in patients with normal and impaired renal functions. Eur J Clin Pharmacol 10:357–365PubMedGoogle Scholar
  189. Rudhardt M, Blauchard P, Fabre J (1978) Accumulation et persistance de aminosides dans le parenchyme renal. Nouv Presse Med 7:3819–3823PubMedGoogle Scholar
  190. Sairio E, Kasanen A, Kangas L, Nieminen AL, Nieminen L (1978) The nephrotoxicity of renal accumulation of amikacin, tobramycin and gentamicin in rats, rabbits and guinea pigs. Exp Pathol (Jena) 15:370–375Google Scholar
  191. Saito A, Katoh Y, Ishikawa K, Uemura H, Tomizawa M, Nakayama I, Satoh K (1978) Studies on sisomicin. Chemotherapy (Tokyo) 26:99–106Google Scholar
  192. Sato K, Hama K (1979) Scanning electron microscopic observations of the under-surface of the tectorial membrane. J Electron Microsc (Tokyo) 28:36–42Google Scholar
  193. Sato K, Koeda T, Yokota M (1979) Histopathological study on the vestibular toxicity of dibekacin and other aminoglycoside antibiotics. J Kanazawa Med Univ 4:172–175Google Scholar
  194. Sawchuk RJ, Zaske DE (1976) Pharmacokinetics of dosing regimes which utilize multiple intravenous infusions; gentamicin in burn patients. J Pharmacokinet Biopharm 4:183–195Google Scholar
  195. Schentag J J (1977) Gentamicin disposition and tissue accumulation on multiple dosing. J Pharmacokinet Biopharm 5:559–577PubMedGoogle Scholar
  196. Schentag J J, Abrutyn E, Jusca WJ (1976) Pharmacokinetic characterization of gentamicin accumulation in man. Clin Pharmacol Ther 19:114Google Scholar
  197. Schentag JJ, Cumbo TJ, Jusco WJ, Plaut ME (1978 a) Gentamicin tissue accumulation and nephrotoxic reactions. J Am Med Assoc 240:1067–2069Google Scholar
  198. Schentag JJ, Lasezkay G, Cumbo TJ, Plaut ME, Jusco WJ (1978 b) Accumulation pharmacokinetics of tobramycin. Antimicrob Agents Chemother 13:649–656PubMedGoogle Scholar
  199. Schentag JJ, Lasezkay G, Plaut ME, Jusco WJ, Cumbo TJ (1978 c) Comparative tissue accumulation of gentamicin and tobramycin in patients. J Antimicrob Chemother 4:23–30PubMedGoogle Scholar
  200. Schrogie J J, Costello R, Hensley MM (1977) Pharmacokinetics of netilmicin in healthy volunteers.Clin Pharmacol Ther 21:116–117Google Scholar
  201. Shiraiwa M (1966) Studies on permanent electrodes implanted on the round window of rabbits. Audiology Jpn 69:631–660Google Scholar
  202. Simon HJ, Yin EJ (1970) Microbioassay of antimicrobial agents. Appl Microbiol 19:573–579PubMedGoogle Scholar
  203. Simon VK, Mösinger EU, Malerczy V (1973) Pharmacokinetic studies of tobramycin and gentamicin. Antimicrob Agents Chemother 3:445–450PubMedGoogle Scholar
  204. Singh YN, Marshall IG, Harrey AL (1978) Some effects of the aminoglycoside antibiotic amikacin on neuromuscular and autonomic transmission. Br J Anaesth 50:109–117PubMedGoogle Scholar
  205. Smith CR, Lipsky J J, Lietman PS (1979) Relationship between aminoglycoside-induced nephrotoxicity and auditory toxicity. Antimicrob Agents Chemother 15:780–782PubMedGoogle Scholar
  206. Spoendlin H, Galogh K (1964) Licht- und elektronenmikroskopische Darstellung von De-hydrogenasen in der Schuche nach Intravitalinkubation. OPL 26:159Google Scholar
  207. Stanley VF, Giesecke AH, Jenkins MT (1969) Neomycin — curare, neuromuscular block and reversal in cats. Anesthesiology 31:228–232PubMedGoogle Scholar
  208. Stevens P, Young LS (1977) Simple method for elimination of aminoglycosides from serum to permit bioassay of other antimicrobial agents. Antimicrob Agents Chemother 12:286–287PubMedGoogle Scholar
  209. Szwed J J, Luft FC, Black HR, Elliot RA, Stuart A (1974) Comparison of the distribution of tobramycin and gentamicin in body fluids of dogs. Antimicrob Agents Chemother 5:444–446PubMedGoogle Scholar
  210. Takabatake H, Oda T, Shiina M, Satoh Y, Ohno T (1978 a) Studies on diffusion of chemo- therapeutic agent into blood, uterine, oviduct, and ovary of rabbits and urinary recovery, of dibekacin and ampicillin. Jpn J Antibiot 31:303–306PubMedGoogle Scholar
  211. Takabatake H, Oda T, Shiina M, Satoh Y, Ohno T (1978 b) Studies on diffusion of chemo- therapeutic agents in uterine muscle, fetus, placenta, amnion, and amniotic fluid of pregnant rabbits, of dibekacin and ampicillin. Jpn J Antibiot 31:307–309PubMedGoogle Scholar
  212. Takeda H, Nakanishi H, Matumura S, Matsuda S, Kawakami M, Otani K, Uno O, Kaneshiro A (1975) Pharmacological studies on tobramycin, effects of tobramycin on cardiovascular, respiratory, muscular, and urinary excretory systems. Chemotherapy (Tokyo) 23:1440–1459Google Scholar
  213. Takimoto M, Fujita K, Maruyama S, Yoshida H (1976) Safety test of lividomycin. III. Experimental study of the cochlear damage induced by lividomycin. Pharmacometrics 6:845–855Google Scholar
  214. Tamura H, Fukakusa Y, Ogawa Y, Ouchi J (1972) The pharmacokinetics of tobramycin following intramuscular administration in new born infants. Chemotherapy (Tokyo) 24:1268–1271Google Scholar
  215. Tan JS, Salstrom SJ (1977) Levels of carbenicillin, ticarcillin, cephalothin, cefazolin, cefa- mandole, gentamicin, tobramycin, and amikacin in human serum and interstitial fluid. Antimicrob Agents Chemother 11:698–700PubMedGoogle Scholar
  216. Tanaka Y, Asanuma A, Yanagisawa K, Katsuki Y (1975) Microphonic and D.C. potentials in the organ of corti and tectrial membrane. Audiology Jpn 18:241–245Google Scholar
  217. Tasaki I, Davis H, Eldredge DH (1954) Exploration of cochlear potentials in guinea pigs with microelectrode. J Acoust Soc Am 26:765–773Google Scholar
  218. Thuillier C, Fillastre JP, Godin M (1977) Pharmacokinetic data on single dose of 280 mg gentamicin i. m. J Antimicrob Chemother 3:527–528PubMedGoogle Scholar
  219. Toyoda Y, Tachibana M (1978) Tissue levels of kanamycin in correlation with oto- and nephrotoxicity. Acta Otolaryngol (Stockh) 86:9–14Google Scholar
  220. Tronovec T (1978) Pharmacokinetics of gentamicin administered intratrancheally to rats. Antimicrob Agents Chemother 14:165–167Google Scholar
  221. Tulkens P, Trouet A (1978) The uptake and intracellular accumulation of aminoglycoside antibiotics in lysosomes of cultures rat fibroblasts. Biochem Pharmacol 27:415–424PubMedGoogle Scholar
  222. Ueda Y (1969) Nephrotoxicity of antibiotics. Chemotherapy (Tokyo) 17Google Scholar
  223. Ueda Y, Nakamura N (1968) Nephrotoxicity of antibiotics. Farumashia 4:179–183Google Scholar
  224. Ueda Y, Saitoh A, Uchiura G (1975) Nephrotoxicity of antibiotics. Gekkan Yakuji 17:35–39Google Scholar
  225. Umemura K, Komiya I, Nakadori S, Sien-Yao Chow (1977) Pharmacokinetics of dibekacin after intramuscular administration in man. Jpn J Antibiot 30:650–656PubMedGoogle Scholar
  226. Umezawa H (1964) Aminoglycoside antibiotics. In: Umezawa H (ed) Recent advances in chemistry and biochemistry of antibiotics. Nissin Tosho Insatsu, Tokyo, pp 67–84Google Scholar
  227. Umezawa I, Ogawa H, Kawakubo Y, Morino T, Nishiyama Y (1976 a) Studies on acute and subacute toxicity of spectinomycin dihydrocloride pentahydrate. J Antibiot (Tokyo) 29:43–54Google Scholar
  228. Umezawa I, Ogawa H, Komiyama K, Kawakubo Y, Morino T, Nishiyama Y (1976 b) Studies on chronic toxicity of spectinomycin dihydrochloride pentahydrate. Jpn J Antibiot 29:55–60PubMedGoogle Scholar
  229. Vogelstein B, Kowarski AA, Lietman PS (1977 a) Continuous sampling as a pharmacokinetic tool. Clin Pharmacol Ther 22:131–139PubMedGoogle Scholar
  230. Vogelstein B, Kowarski A A, Lietman PS (1977 b) The pharmacokinetics of amikacin in children. J Pediat 91:333–339PubMedGoogle Scholar
  231. Wagman GH, Oden EM, Weinstein MJ, Irwin S (1967) Effect of calcium on the toxicity of gentamicin. Antimicrob Agents Chemother 1966:175–181Google Scholar
  232. Waitz J A, Moss EL Jr, Weinstein MJ (1971) Aspects of the chronic toxicity of gentamicin sulfate in cats. J Infect Dis 124:125–129Google Scholar
  233. Waksman SA (1949) Clinical use of streptomycin. Streptomycin, nature and practical application. Williams &Wilkins, Baltimore, pp 279–560Google Scholar
  234. Walker JM, Wise R, Mitchard M (1979) The pharmacokinetics of amikacin and gentamicin in volunteers: a comparison of individual differences. J Antimicrob Chemother 5:95–99PubMedGoogle Scholar
  235. Watanabe Y, Nakajima R, Oda R, Uno M, Naitoh T (1971) Experimental study on the transfer of kanamycin to the inner ear fluids. Med J Osaka Univ 21:257–263PubMedGoogle Scholar
  236. Watanuki K, Gottesberg AM (1971) Toxic effects of streptomycin and kanamycin upon the sensory epithelium of thecrista ampullaris. Acta Otolaryngol (Stockh) 72:59–67Google Scholar
  237. Watson EH, Stow RM (1948) Streptomycin therapy, effects on fetus. J Am Med Assoc 137:1599–1600PubMedGoogle Scholar
  238. Wefer G, Bray C (1930) The nature of acoustic response. J Exp Physiol 13:373Google Scholar
  239. Weinstein L (1970) Chemotherapy of microbial disease. In: Goodman LS; Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York Toronto London, pp 1090–1247Google Scholar
  240. Weitnauer G, Mattei A, Sinoncini F (1957) Acute and chronic toxicity of some complex salts of streptomycin and dihydrostreptomycin. Farmaco [Sci] 12:899–927Google Scholar
  241. Whelton A, Carter GG, Walker WG (1975) Gentamicin concentrations in healthy and diseased kidneys. Clin Rev 23:225AGoogle Scholar
  242. Whelton A, Carter GG, Bryant HH, Fox L, Walker WG (1976) Therapeutic implications of gentamicin accumulation in severely diseased kidneys. Arch Intern Med 136:172–176PubMedGoogle Scholar
  243. West BA, Brummett RE (1973) Interaction of kanamycin and ethacrynic acid. Arch Otolaryngol 98:32–37PubMedGoogle Scholar
  244. Yamada H, Yoshida T, Hirano K, Kimura Y, Ichihashi T, Doi M, Konaka J, Katagiri K (1975) Absorption, excretion, distribution and metabolism of tobramycin. Chemotherapy (Tokyo) 23:894–899Google Scholar
  245. Yamamoto K, Yoshimura K, Hirono S, Inoue Y, Sakamori M, Matsumura S, Morishige E (1975) The effects of tobramycin on the central nervous system. Chemotherapy (Tokyo) 23:1460–1469Google Scholar
  246. Yamasaku F (1974) Nephrotoxicity. Chemotherapy (Tokyo) 22:210–213Google Scholar
  247. Yamasaku F, Kabasawa T (1976) Serum levels of dibekacin in normal subjects and uremic patients following intramuscular injections. Chemotherapy (Tokyo) 24:1515–1520Google Scholar
  248. Yamasaku F, Suzuki Y, Umemura K (1980) Pharmacokinetics of ribostamycin in healthy volunteers and patients with impaired renal function. Jpn J Antibiot 33:1318–1331PubMedGoogle Scholar
  249. Yamashita T (1972) Histochemical studies on the effects of oxygen deprivation in the hair cells of the cortis organ. Otol Fukuoka 65:591–613Google Scholar
  250. Yokota M (1977) Ototoxic effects of some aminoglycoside antibiotics on the inner ear in guinea pigs. J Showa Medical 37:535–544Google Scholar
  251. Yokota M, Odaki M, Koeda T, Sato K, Akiyoshi M (1976) The safety evaluation of fradi-omycin-gramicidin-S troches “Meiji”. Jpn J Antibiot 29:841–849PubMedGoogle Scholar
  252. Yokota M, Odaki M, Koeda T, Sato K (1977) Ototoxic effects of some aminoglycoside antibiotics on the inner ear in the spontaneously hypertensive rats (SHR). Jpn J Antibiot 30:738–743PubMedGoogle Scholar
  253. Yoshida M, Kimura Y, Doi M, Katagiri K (1975) Micromethod for microbiological assay of to bramycin concentrations in body fluids. Chemotherapy (Tokyo) 23:886–893Google Scholar
  254. Yoshioka H, Takimoto M, Nakatsugawa T, Maeda T, Tasaka Y (1974) Pharmacokineticsand clinical evaluation of BB-K8 in children. Jpn J Antibiot 27:382–388PubMedGoogle Scholar
  255. Ziv G, Sulman FG (1972) Binding of antibiotics to bovine and ovine serum. Antimicrob Agents Chemother 2:206–213PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1982

Authors and Affiliations

  • T. Koeda
  • K. Umemura
  • M. Yokota

There are no affiliations available

Personalised recommendations