Translocation of Drugs and Other Exogenous Chemicals into Adipose Tissue

  • Lester C. Mark
Part of the Handbuch der experimentellen Pharmakologie/Handbook of Experimental Pharmacology book series (HEP, volume 28 / 1)

Abstract

The role of adipose tissue in the pharmacokinetics of drugs and other substances introduced deliberately or inadvertently into the body is modulated by a variety of factors. The list includes (a) the physicochemical characteristics of the invading material, (b) the blood flow to adipose tissue, (c) the total mass of adipose tissue in the body, (d) the affinity of adipose tissue for the substance introduced, and (e) other special factors.

Keywords

Hull Diazepam Halothane Biotransformation Phenobarbital 

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References

  1. Axelrod, J., Aronow, L., Brodie, B.B.: The physiological disposition and biotransformation of dibenamine and a method for its estimation in biological tissues. J. Pharmacol, exp. Ther. 106, 166 — 179 (1952).Google Scholar
  2. Bischoff, K.B., Dedrick, R.L.: Thiopental pharmacokinetics. J. pharm. Sci. 57, 1346 — 1351 (1968).CrossRefGoogle Scholar
  3. Brand, L., Hyman, A. I., Landrau, M. A., Mark, L. C., Perel, J.M.: Effects of environmental temperature on uptake of thiopental by brown adipose tissue and brain. Abstracts of scientific papers, 1969 Annual Meeting. San Francisco: American Society of Anesthesiologists 1969.Google Scholar
  4. Brand, L., Hyman, A. I., Landrau, M. A., Mark, L.C., Perel, J.M., Burns, J. J., Dayton, P.G., Taller, D., Papper, E.M.: Physiological disposition of methitural in man. Med. Exp. 1, 339 — 33 (1959).Google Scholar
  5. Brand, L., Hyman, A. I., Landrau, M. A., Mark, L.C., Perel, J.M., Burns, J. J., Taller, D., Snell, M. Mcm., Vrindten, P., Dayton, P. G., Papper, E.M.,: Physiologic disposition of methohexital in man. Anesthesiology 24, 331 — 335 (1963).Google Scholar
  6. Brodie, B. B.: Physiological disposition and chemical fate of thiobarbiturates in the body. Fed. Proc. 11, 632 — 639 (1952).PubMedGoogle Scholar
  7. Brodie, B. B., Aronow, L., Axelrod, J.: The fate of Dibenzyline in the body and the role of fat in its duration of action. J. Pharmacol, exp. Ther. Ill, 21 — 29 (1954).Google Scholar
  8. Brodie, B. B., Bernstein, E., Mark, L.C.: The role of body fat in limiting the duration of action of thiopental. J. Pharmacol, exp. Ther. 105, 421 — 426 (1952).Google Scholar
  9. Brodie, B. B., Hogben, C.A.M.: Some physicochemical factors in drug action. J. Pharm. Pharmacol. 9, 345 — 380 (1957).PubMedCrossRefGoogle Scholar
  10. Brodie, B. B., Mark, L.C., Papper, E.M., Lief, P. A., Bernstein, E., Rovenstine, E.A.: The fate of thiopental in man and a method for its estimation in biological material. J. Pharmacol, exp. Ther. 98, 85 — 96 (1950).Google Scholar
  11. Carlson, L.A., Hanngren, A.: Initial distribution in mice of 3H-labeled nicotinic acid, studied with autoradiography. Life Sci. 3, 867 — 871 (1964).PubMedCrossRefGoogle Scholar
  12. Casarett L. J., Fryer, G.C., Yatjger, W.L., Jr., Klemmen, H.W.: Organochlorine pesticide residue in human tissue. Hawaii Arch, environm. Hlth 17, 306 — 311 (1968).Google Scholar
  13. Cassano, G.B., Gatti, B., Gliozzi, E., Hansson, E.: Autoradiographic distribution study of “short-acting” and “long-acting” barbiturates: 35S-thiopentone and 14C-phenobarbitone. Brit. J. Anaesth. 39, 11 — 20 (1967).PubMedCrossRefGoogle Scholar
  14. Cohen, E.N., Hood, N.: Application of low-temperature autoradiography to studies of the uptake and metabolism of volatile anesthetics in the mouse. 1. Chloroform. Anesthesiology 30, 306 — 314 (1969).CrossRefGoogle Scholar
  15. Conney, A.H.: Pharmacological implications of enzyme induction. Pharmacol. Rev. 19, 317 — 366 (1967).PubMedGoogle Scholar
  16. Cueto, C., Jr., Hayes, W.J., Jr.: Effect of phenobarbital on the metabolism of Dieldrin. Toxicol, appl. Pharmacol. 7, 481 (1965).Google Scholar
  17. Davson, H., Eggleton, M.G.: Starling and Lovatt Evans principles of human physiology. Philadelphia: Lea & Febiger 1968.Google Scholar
  18. Dawkins, M.J.R., Hull, D.: Brown adipose tissue and the response of newborn rabbits to cold. J. Physiol. (Lond.) 172, 216 — 238 (1964).Google Scholar
  19. Dayton, P.G., Perel, J.M., Landrau, M.A., Brand, L., Mark, L.C.: The relationship between binding of thiopental to plasma and its distribution into adipose tissue in man, as measured by a spectrophotofluorometric method. Biochem. Pharmacol. 16, 2321 — 2326 (1967).CrossRefGoogle Scholar
  20. Demyttenaere, M.H., Schoenfeld, L., Maher, J.F.: Treatment of glutethimide poisoning. A comparison of forced diuresis and dialysis. J. Amer. med. Ass. 203, 885 — 887 (1968).CrossRefGoogle Scholar
  21. Dundee, J.W.: Clinical pharmacology of general anesthetics. Clin. Pharmacol. Ther. 8, 91 — 123 (1967).Google Scholar
  22. Gilbert, D., Goldberg, L.: Liver response tests. III. Liver enlargement and stimulation of microsomal processing enzyme activity. Food Cosmet. Toxicol. 3, 417 — 432 (1965).Google Scholar
  23. Goldbaum, L.R., Williams M.A., Johnston, E.H.: Determination and distribution of Doriden. J. forens. Sci. 7, 499 — 503 (1962).Google Scholar
  24. Goldstein, A., ARONOW, L.: The durations of action of thiopental and pentobarbital. J. Pharmacol, exp. Ther. 128, 1 — 6 (1960).Google Scholar
  25. Hayes, W.J., Jr.: Toxicity of pesticides to man: risks from present levels. Proc. roy. Soc. B 167, 101 — 127 (1967).Google Scholar
  26. Hayes, W.J., Jr., Durham, W. F., Cueto, C., Jr.: The effect of known repeated oral doses of chlorophenothane (DDT) in man. J. Amer. med. Ass. 162, 890 — 897 (1956).Google Scholar
  27. Heim, T., Hull, D.: The blood flow and oxygen consumption of brown adipose tissue in the newborn rabbit. J. Physiol. (Lond.) 186, 42 — 55 (1966).Google Scholar
  28. Hoffman, W. S., Adler, H., Fishbein, W. I., Bauer, F. C.: Relation of pesticide concentration in fat to pathological changes in tissues. Arch, environm. Hlth 15, 758— 765 (1967).Google Scholar
  29. Hunter, C.G., Robinson, J.: Aldrin, Dieldrin and man. Food Cosmet. Toxicol. 6, 253 — 260 (1968).Google Scholar
  30. Hunter, C.G., Pharmacodynamics of Dieldrin (HEOD). I. Ingestion by human subjects for 18 months. Arch, environm. Hlth 15, 614 — 626 (1967).Google Scholar
  31. Hunter, C.G., Jager, K.W.: Aldrin and Dieldrin — The safety of present exposures of the general populations of the United Kingdom and the United States. Food Cosmet. Toxicol. 5, 781 — 787 (1967).Google Scholar
  32. Hunter, C.G., Roberts, M.: Pharmacodynamics of Dieldrin (HEOD). Ingestion by human subjects for 18 to 24 months, and postexposure for eight months. Arch, environm. Hlth 18, 12 — 21 (1969).Google Scholar
  33. Keberle, H., Hoffmann, K., Bernhard, K.: The metabolism of glutethimide (Doriden). Experientia (Basel) 18, 105 — 111 (1962).CrossRefGoogle Scholar
  34. Larsen, O.A., Lassen, N.A.: Fatty tissue blood flow measured by xenon—133 clearance. Scand. J. clin. Lab. Invest. 99, 46 — 49 (1967).Google Scholar
  35. Quaade, F.: Blood flow through human adipose tissue determined with radioactive xenon. Acta physiol. scand. 66, 337 — 345 (1966).PubMedCrossRefGoogle Scholar
  36. Van Loon, E. J., Quoted by C.H. Williams: Drug-pesticide interactions. FDA Papers 3, (7) 14 — 17 (1969).Google Scholar
  37. Lundin, G.: Nitrogen elimination from the tissues during oxygen breathing and its relationship to the fat: muscle ratio and the localization of bends. J. Physiol. (Lond.) 152, 167 — 175 (1960).Google Scholar
  38. Marcucci, F., Fanelli, R., Frova, M., Morselli, P.L.: Levels of diazepam in adipose tissue of rats, mice and man. Europ. J. Pharmacol. 4, 464 — 466 (1968).CrossRefGoogle Scholar
  39. Mark, L.C.: Thiobarbiturates. In: Uptake and distribution of anesthetic agents. New York: McGraw-Hill 1963.Google Scholar
  40. Mark, L.C., Brand, L.: Where does the Pentothal go ? Bull. N.Y. Acad. Med. 40, 476 — 482 (1964).PubMedGoogle Scholar
  41. Mark, L.C., Lief, P.A., Papper, E.M., Rovenstine, E.A., Brodie, B.B., Bernstein, E.: The fate of Pentothal in man. Fed. Proc. 8, 318 (1949a).Google Scholar
  42. Mark, L.C., Papper, E.M., Brodie, B.B., Rovenstine, E.A.: Quantitative pharmacologic studies with Pentothal. N. Y. St. J. Med. 49, 1546 — 1549 (1949b).Google Scholar
  43. Mark, L.C., Perel, J. M., Brand, L., Dayton, P. G.: Studies with thiohexital, an anesthetic barbiturate metabolized with unusual rapidity in man. Anesthesiology 29, 1159 — 1166 (1968).PubMedCrossRefGoogle Scholar
  44. Mark, L.C., Distribution and metabolism of thiohexital. Anesthesiology 31, 384 — 385 (1969).CrossRefGoogle Scholar
  45. Mcmasters, V., Howard, T., Kinsell, L.W., Vanderveen, J., Olcott, H.S.: Tocopherol storage and depletion in adipose tissue and plasma of normal and diabetic human subjects. Amer. J. clin. Nutr. 20, 622 — 626 (1967).PubMedGoogle Scholar
  46. Meli, A., Honrath, W.L., Wolff, A.: Mechanism by which 3-enol etherification enhances the oral activity of methyl testosterone in rats. Endocrinology 74, 79 — 82 (1964).PubMedCrossRefGoogle Scholar
  47. Meli, A., Steinetz, B. G., Giannina, T.: Fat storage, de-etherification and elimination of Quinestrol in the rat as influenced by route of administration. Proc. Soc. exp. Biol. (N.Y.) 127, 1042 — 1048 (1968).Google Scholar
  48. Meli, A., Wolff, A., Honrath, W.L.: The mechanism by which 3-etherification with cyclopentyl alcohol enhances the oral activity of ethinylestradiol. Steroids 2, 417 — 424 (1963).CrossRefGoogle Scholar
  49. Morse, W.L, Soeldner, J.S.: The composition of adipose tissue and the nonadipose body of obese and nonobese man. Metabolism 12, 99 — 107 (1963).Google Scholar
  50. Morse, W.L, The measurement of human adipose tissue mass. Chapter 65 in: Handbook of physiology, Section 5: Adipose tissue. Washington, D.C.: American Physiological Society 1965.Google Scholar
  51. Mountcastle, V.B.: Medical physiology, 12th ed. St. Louis: Mosby 1968.Google Scholar
  52. Papper, E.M., Peterson, R.C., Burns, J.J., Bernstein, E., Lief, P.A., Brodie, B.B.: Physiological disposition of certain N-alkylthiobarbiturates. Anesthesiology 16, 544 — 550 (1955).PubMedCrossRefGoogle Scholar
  53. Peakall, D.B.: Pesticide-induced enzyme breakdown of steroids in birds. Nature (Lond.) 216, 505 — 506 (1967).CrossRefGoogle Scholar
  54. Perl, W., Lesser, G.T., Steele, J.M.: The kinetics of distribution of the fat-soluble inert gas cyclopropane in the body. Biophys. J. 1, 111 — 125 (1960).PubMedCrossRefGoogle Scholar
  55. Perl, W., Rackow, H., Salanitre, E., Wolf, G.L., Epstein, R.M.: Intertissue diffusion effect for inert fat-soluble gases. J. appl. Physiol. 20, 621 — 627 (1965).PubMedGoogle Scholar
  56. Plough, I.C., Waldstein, S.S., Barila, T.G., Goldbaum, L.R.: The rate of disappearance of thiopental from the plasma in the dog and in man. J. Pharmacol, exp. Ther. 116, 486 — 489 (1956).Google Scholar
  57. Price, H.L.: A dynamic concept of the distribution of thiopental in the human body. Anesthesiology 21, 40 — 45 (1960).PubMedCrossRefGoogle Scholar
  58. Price, H.L., Kovnat, P. J., Safer, J.N., Conner, E.H., Price, M.L.: The uptake of thiopental by body tissues and its relation to the duration of narcosis. Clin. Pharmacol. Ther. 1, 16 — 22 (1960).Google Scholar
  59. Price, H.L., Radomski, J.L., Deichman, W.B., Clizer, E.E., Rey, A.: Pesticide concentrations in the liver, brain and adipose tissue of terminal hospital patients. Food Cosmet. Toxicol. 6, 209 — 220 (1968).Google Scholar
  60. Price, H.L., Robinson, J.: Dynamics of organochlorine insecticides in vertebrates and ecosystems. Nature (Lond.) 215, 33 — 35 (1967).CrossRefGoogle Scholar
  61. Price, H.L., The burden of chlorinated hydrocarbon pesticides in man. Canad. med. Ass. J. 100, 180 — 191 (1969).Google Scholar
  62. Price, H.L., Persistent pesticides. Ann. Rev. Pharmacol. 10, (In Press) (1970).Google Scholar
  63. Price, H.L., Richardson, A., Hunter, C.G., Crabtree, A.N., Rees, H. J.: Organochlorine insecticide content of human adipose tissue in south-eastern England. Brit. J. industr. Med. 22, 220 — 229 (1965).Google Scholar
  64. Price, H.L., Roberts, M.: Accumulation, distribution and elimination of organochlorine insecticides by vertebrates. In: Physico-chemical and biophysical factors affecting the activity of pesticides, Monograph no. 29. London: Soc. Chem. Industry 1968.Google Scholar
  65. Saidman, L. J., Eger, E.I. II: The effect of thiopental metabolism on duration of anesthesia. Anesthesiology 27, 118 — 126 (1966).PubMedCrossRefGoogle Scholar
  66. Schwartz, M.A., Koechlin, B.A., Postma, E., Palmer, S., Krol, G.: Metabolism of diazepam in rat, dog and man. J. Pharmacol, exp. Ther. 149, 423 — 435 (1965).Google Scholar
  67. Shear, C., Clayton, C.E., Barry, K.G., Knowlton, F.M., Goldbaum, L.R.: Dialysis for intoxication with lipid soluble drugs: enhancement of glutethimide extraction with lipid dialysate. Trans. Amer. Soc. artif. intern. Org. 11, 173 — 177 (1965).Google Scholar
  68. Shideman, F.E., Gould, T.C., Winters, W.D., Peterson, R.C., Wilner, W.K.: The distribution and in vivo rate of metabolism of thiopental. J. Pharmacol, exp. Ther. 107, 368 — 378 (1953).Google Scholar
  69. Shinaberger, J.H., Shear, L., Clayton, L.E., Barry, K.G., Knowlton, M., Goldbaum, L.R.: Intraperitoneal lipid: enhancement of glutethimide extraction during peritoneal dialysis. Clin. Res. 13, 54 (1965).Google Scholar
  70. Street, J.C.: DDT antagonism to Dieldrin storage in adipose tissue of rats. Science 146, 1580 — 1581 (1964).PubMedCrossRefGoogle Scholar
  71. Street, J.C., Wang, M., Blau, A.D.: Drug effects on Dieldrin storage in rat tissue. Bull, environm. Contam. Toxicol. 1, 6 — 15 (1966).CrossRefGoogle Scholar
  72. De Vlieger, M., Robinson, J., Crabtree, A.N., VAN DIJK, M.C.: The organochlorine insecticide content of human tissues. Arch, environm. Hlth 17, 759 — 767 (1968).Google Scholar
  73. Weisberg, H. F.: Water, electrolyte and acid-base balance, 2nd ed. Baltimore: Williams and Wilkins 1962.Google Scholar
  74. Wertheimer, H.E.: Introduction — a perspective. In: Handbook of physiology, Section 5, Adipose tissue. Washington, D. C.: American Physiological Society 1965.Google Scholar
  75. Woodwell, G.M., Wurster, C.F., Isaacson, B.A.: DDT residues in an east coast estuary: a case of biological concentration of a persistent insecticide. Science 156, 821 — 824 (1967).CrossRefGoogle Scholar
  76. Wulfsohn, M.L., Joshi, C.W.: Thiopentone dosage based on lean body mass. Brit. J. Anaesth. 41, 516 — 521 (1969).CrossRefGoogle Scholar

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© Springer-Verlag Berlin · Heidelberg 1971

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  • Lester C. Mark

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