Clinical Pharmacokinetics

, Volume 18, Issue 2, pp 168–175 | Cite as

Increased Renal Clearance of Cefsulodin Due to Higher Glomerular Filtration Rate in Cystic Fibrosis

  • Ann Hedman
  • Gunnar Alván
  • Birgitta Strandvik
  • Annie Arvidsson
Original Research Article

Summary

The steady-state renal clearance of cefsulodin was studied in 6 patients with cystic fibrosis and 8 healthy controls. The drug was administered by constant rate infusion to obtain 2 values of plasma concentration, 2 and 30 mg/L. As an estimate of the glomerular filtration rate, the renal clearance of inulin was measured simultaneously.

The results showed the figures for inulin clearance to be approximately 30% higher in cystic fibrosis patients than in healthy controls at both concentrations, and a corresponding increase in the renal clearance of cefsulodin was seen in patients over controls. The ratio between the renal clearances of the 2 substances was on average 0.9 in both groups.

The correlation found between the 2 renal clearances (r = 0.75; p < 0.001) indicates that glomerular filtration rate has considerable influence on the renal elimination of cefsulodin. This finding emphasises the importance of glomerular filtration rate for the renal clearance of drugs in cystic fibrosis.

Keywords

High Performance Liquid Chromatograph Cystic Fibrosis Glomerular Filtration Rate Renal Clearance Cystic Fibrosis Patient 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aladjem M, Lotan D, Boichis H, Orda S, Katznelson D. Renal function in patients with cystic fibrosis. Nephron 34: 84–86, 1983PubMedCrossRefGoogle Scholar
  2. Arvidsson A, Alván G, Strandvik B. Difference in renal handling of cefsulodin between patients with cystic fibrosis and normal subjects. Acta Paediatrica Scandinavica 72: 293–294, 1983PubMedCrossRefGoogle Scholar
  3. Assael BM, Marra G, Tirelli AS, Cavanna G, Claris Appiani A, et al. Renal function in cystic fibrosis. International Journal of Pediatric Nephrology 7: 213–216, 1986PubMedGoogle Scholar
  4. Berg U, Kusoffsky E, Strandvik B. Renal function in cystic fibrosis with special reference to the renal sodium handling. Acta Paediatrica Scandinavica 71: 833–838, 1982PubMedCrossRefGoogle Scholar
  5. Blantz CR, Pelayo JC. A functional role for the tubulo-glomerular feedback mechanism. Kidney International 25: 739–746, 1984PubMedCrossRefGoogle Scholar
  6. Carlstedt-Duke J, Bronnegard M, Strandvik B. Pathological regulation of arachidonic acid release in cystic fibrosis: the putative basic defect. Proceedings of the National Academy of Sciences 83: 9202–9206, 1986CrossRefGoogle Scholar
  7. de Groot R, Smith AL, Antibiotic pharmacokinetics in cystic fibrosis. Differences and clincial significance. Clinical Pharmacokinetics 13: 228–253, 1987PubMedCrossRefGoogle Scholar
  8. Finkelstein E, Hall K. Aminoglycoside clearance in patients with cystic fibrosis. Journal of Pediatrics 94: 163–164, 1979PubMedGoogle Scholar
  9. Gibson TP, Granneman GR, Kallal JE, Sennello LT. Cefsulodin kinetics in renal impairment. Clinical Pharmacology and Therapeutics 31: 602–608, 1982PubMedCrossRefGoogle Scholar
  10. Granneman GR, Sennello LT. Precise high-performance liquid Chromatographic procedure for the determination of cefsulodin, a new antipseudomonal cephalosporin antibiotic, in plasma. Journal of Pharmaceutical Sciences 71: 1112–1115, 1982PubMedCrossRefGoogle Scholar
  11. Granneman GR, Sennello LT, Sonders RC, Wynne B, Thomas EW. Cefsulodin kinetics in healthy subjects after intramuscular and intravenous injection. Clinical Pharmacology and Therapeutics 31: 95–103, 1982PubMedCrossRefGoogle Scholar
  12. Hedman A, Adan-Abdi Y, Alván G, Strandvik B, Arvidsson A. Influence of the glomerular filtration rate on renal clearance of ceftazidime in cystic fibrosis. Clinical Pharmacokinetics 15: 57–65, 1988PubMedCrossRefGoogle Scholar
  13. Hilger HH, Klumper JD, Ullrich KJ. Wasserruckresorption und Jonentransport durch die Sammelsrohrzellen der Saugetierniere. Pflugers Archiv — European Journal of Physiology 267: 218–237, 1958PubMedCrossRefGoogle Scholar
  14. Jusko WJ, Mosovich LL, Gerbracht LM, Mattar ME, Yaffe SJ. Enhanced renal excretion of dicloxacillin in patients with cystic fibrosis. Pediatrics 56: 1038–1044, 1975PubMedGoogle Scholar
  15. Leeder JS, Spino M, Isles AF, Tesoro AM, Gold R, et al. Ceftazidime disposition in acute and stable cystic fibrosis. Clinical Pharmacology and Therapuetics 36: 355–362, 1984CrossRefGoogle Scholar
  16. Matzke GR, Keane WF. Cefsulodin pharmacokinelics in patients with various degrees of renal function. Antimicrobial Agents and Chemotherapy 23: 369–373, 1983PubMedCrossRefGoogle Scholar
  17. McPherson MA, Dormer RL. The molecular and biochemical basis of cystic fibrosis. Bioscience Reports 7: 167–185, 1987PubMedCrossRefGoogle Scholar
  18. Reed MD, Stern RC, Yamashita TS, Ackers J, Myers CM, et al. Single-dose pharmacokinetics of cefsulodin in patients with cystic fibrosis. Antimicrobial Agents and Chemotherapy 25: 579–581, 1984PubMedCrossRefGoogle Scholar
  19. Robson AM, Tateishi S, Ingelfinger JR, Strominger DB, Klahr S. Renal function in patients with cystic fibrosis. Journal of Pediatrics 79: 42–50, 1971PubMedCrossRefGoogle Scholar
  20. Schachter SH. Spino M. Isles AF. Tesoro A, Prober C. et al. Pharmacokinetics of cefoperazone in patients with cystic fibrosis and healthy volunteers. Proceedings of the 13th International Congress of Chemotherapy. Vienna, August 28–September 2, 1983, pp. 45–48, 1983Google Scholar
  21. Schoeller J. Fillastre J. Humbert G, Lecaillon JB. Pharmacokinetics of cefsulodin in patients with renal insufficiency. In Periti & Grassi (Eds) Current chemotherapy and immunotherapy, pp. 526–527, American Society for Microbiology, Washington, D.C. 1982Google Scholar
  22. Shwachman H, Kulczycki LL. Long-term study of one hundred five patients with cystic fibrosis: studies made over a five- to fourteen-year period. American Journal of Diseases of Children 96: 6–16, 1958Google Scholar
  23. Spino M, Chai RP, Isles AF, Balfe JW, Brown RG, et al. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis. Journal of Pediatrics 107: 64–70, 1985PubMedCrossRefGoogle Scholar
  24. Spino M, Chai RP, Isles AF, Thiessen JJ, Tesoro A, et al. Cloxacillin absorption and disposition in cystic fibrosis. Journal of Pediatrics 105: 829–835, 1984PubMedCrossRefGoogle Scholar
  25. Strandvik B, Bronnegård M. Carlstedt-Duke J. Arachidonic acid release in CF. In Mastella & Quinton (Eds) Cellular and molecular basis of cystic fibrosis, pp. 445–450, San Francisco Press, California, 1988Google Scholar
  26. Strandvik B, Bronnegård M, Gilljam H, Carlstedt-Duke J. Relation between defective regulation of arachidonic acid release and symptoms in cystic fibrosis. Scandinavian Journal of Gastroenterology 23(Suppl. 143): 1–4, 1988CrossRefGoogle Scholar
  27. Strandvik B, Ellin A. Gilljam H. Kallner A. Wiman LG. Fatty acid metabolism in cystic fibrosis. In Warwick (Ed) 1000 years of cystic fibrosis. p. 304. University of Minnesota. 1981Google Scholar
  28. Talamo RC. Rosenstein BJ, Berninger RW. Cystic fibrosis. In Stanbury et al. (Eds) The metabolic basis of inherited disease, pp. 1899–1917, McGraw Hill, New York. 1983Google Scholar
  29. Yaffe SJ, Gerbracht LM, Mosovich LL, Mattar ME, Danish M, et al. Pharmacokinetics of methicillin in patients with cystic fibrosis. Journal of Infectious Diseases 35: 828–831, 1977CrossRefGoogle Scholar
  30. Zak O, Konopka EA, Tosch W, Ahrens T, Zimmerman W, et al. Experimental evaluation of CGP 7174/E (SCE 129). a new injectable cephalosporin antibiotic active against pseudomonas aeruginosa. Drugs Under Experimental and Clinical Research 5: 45–59, 1979Google Scholar

Copyright information

© ADIS Press Limited 1990

Authors and Affiliations

  • Ann Hedman
    • 1
  • Gunnar Alván
    • 1
  • Birgitta Strandvik
    • 1
  • Annie Arvidsson
    • 1
  1. 1.Departments of Clinical Pharmacology and Pediatrics, Karolinska InstitutetHuddinge University HospitalHuddingeSweden

Personalised recommendations