Species differences are a major obstacle in predicting toxicity of xenobiotics from one species to another. Species differences in toxicity of drugs and other chemicals may be due to differences in pharmacokinetics or pharmacodynamics. This paper illustrates the point that species differences in pharmacokinetics of xenobiotics may be the result of differences in any of the processes contributing to the disposition of a xenobiotic. This is an important point because biotransformation as a cause of species differences for the disposition of xenobiotics has been overemphasized in the past, whereas only scant attention has been paid to the other 3 major contributing processes to disposition, viz. absorption, distribution, and excretion. This brief overview presents a balanced examination of all 4 major processes (absorption, distribution, biotransformation and excretion) as they affect the pharmocokinetics of xenobiotics in various species.
References
1.
1. Batra VF, Morrison JF, Woodward DF, Siverd NS, and Yacobi A (1986). Pharmacokinetics of mitoxantrone in man and laboratory animals.Drug Metab. Rev.17: 311–329.
2.
2. Calabrese EJ (1984). Gastrointestinal and dermal absorption: Interspecies differences.Drug Metab. Rev.15: 1013–1032.
3.
3. Caldwell J (1981). The current status of attempts to predict species differences in drug metabolism.Drug Metab. Rev.12: 221–237.
4.
4. Caldwell J (1982). Conjugation reactions in foreign-compound metabolism: Definition, consequences and species variations.Drug Metab. Rev.13: 745–777.
5.
5. Cayen MN (1980). Metabolic disposition of antihy-perlipidemic agents in man and laboratory animals.Drug Metab. Rev.11: 291–323.
6.
6. DiCarlo FJ (1984). Carcinogenesis bioassay data: Correlation by species and sex.Drug Metab. Rev.15: 409–13.
7.
7. DiCarlo FJ and Fung VA (1984). Summary of carcinogenicity data generated by the National Cancer Institute/National Toxicology Program.Drug Metab. Rev.15: 1251–1273.
8.
8. Dreyfuss J, Shaw JM, and Ross JJ (1978). Absorption of the α-adrenergic-blocking agent, nadolol, by mice, rats, hamsters, rabbits, dogs, monkeys and man: Unusual species differences.Xenobiotica8: 503–510.
9.
9. Dugard PH (1983). Skin permeability theory in relation to measurements of percutaneous absorption in toxicology. In: Dermatotoxicology, 2nd ed., FN Marzulli and HI Maibach (eds). Hemisphere Publ. Corp., Washington/New York/London, pp. 91–116.
10.
10. Freeman R, Rozman K, and Wilson A (1988). Physiological pharmacokinetic model of hexachlorobenzene in the rat.Health Physics (in press).
11.
11. Gregus Z, Watkins JB, Thompson TN, Harvey MJ, Rozman K, and Klaassen CD (1983). Hepatic phase I and phase II biotransformation in quail and trout: Comparison to other species commonly used in toxicity testing.Toxicol. Appl. Pharmacol.67: 430–441.
12.
12. Hallikainen A and Salminen S (1986). Foods, food additives and contaminants in gastrointestinal toxicology. In: Gastrointestinal Toxicology, K Rozman and O Hänninen (eds). Elsevier, Amsterdam/New York/Oxford, pp. 342–362.
13.
13. Hayton WL (1980). Rate-limiting barriers to intestinal drug absorption: A review.J. Pharmacokin. Biopharm.8: 321–334.
14.
14. Hirom PC, Millburn P, and Smith RL (1976). Bile and urine as complementary pathways for the excretion of foreign organic compounds.Xenobiotica6: 55–64.
15.
15. Hucker HB, Hutt JE, White SD, Arison BH, and Zacchei AB (1966). Studies on the absorption, distribution and excretion of indomethacin in various species.J. Pharmacol. Exp. Ther.153: 237–249.
16.
16. Iatropoulos MJ (1986). Morphology of the gastrointestinal tract. In: Gastrointestinal Toxicology, K Rozman and O Hänninen (eds). Elsevier, Amsterdam/ New York/Oxford, pp. 246–266.
17.
17. Kao J, Patterson FU, and Hall J (1985). Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: An in vitro study with benzo[a]pyrene and testosterone.Toxicol. Appl. Pharmacol.81: 502–516.
18.
18. Klaassen CD and Watkins JB III (1984). Mechanisms of bile formation, hepatic uptake and biliary excretion.Pharmacol. Rev.36: 1–67.
19.
19. Kurz H and Fichtl B (1983). Binding of drugs to tissues.Drug Metab. Rev.14: 467–510.
20.
20. Laitinen M and Watkins JB III (1986). Mucosal biotransformations. In: Gastrointestinal Toxicology, K Rozman and O Hänninen (eds). Elsevier, Amsterdam/New York/Oxford, pp. 169–192.
21.
21. Migdalof BH, Antonaccio MJ, McKinstry DN, Singhvi SM, Lan SJ, Egli P, and Kripalani KJ (1984). Captopril: Pharmacology, metabolism and disposition.Drug Metab. Rev.15: 841–869.
22.
22. Neal RA, Olsen JR, Gasiewicz TA, and Geiger LE (1982). The toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mammalian systems.Drug Metab. Rev.13: 355–385.
23.
23. Rozman K and Iatropoulos MJ (1987). Gastrointestinal toxicity: Dispositional considerations. In: Experimental and Clinical Toxicokinetics, A Yacobi and JP Skelly (eds). American Association of Pharmaceutical Scientists, Washington D.C. (in press).
24.
24. Scheufler E and Rozman K (1984). Comparative decontamination of hexachlorobenzene exposed rats and rabbits by hexadecane.J. Toxicol. Environ. Health14: 353–362.
25.
25. Shanker LS (1962). Passage of drugs across body membranes.Pharmacol. Rev.14: 501–530.
26.
26. Smith HW (1965). Observations on the flora of the alimentary tract of animals and factors affecting its composition.J. Pathol. Bacteriol.89: 95–107.
27.
27. Smith RP (1986). Toxic responses of the blood. In: Casarett and Doull's Toxicology, 3rd ed., CD Klaassen, MO Amdur, and J Doull (eds). Macmillan Publishing Co., New York/Toronto/London, pp. 223–244.
28.
28. Smith GS (1986). Gastrointestinal toxifications and detoxifications in relation to resource management. In: Gastrointestinal Toxicology, K Rozman and O Hänninen (eds). Elsevier, Amsterdam/New York/Oxford, pp. 505–516.
29.
29. Symchowicz S, Staub MS, and Wong KK (1967). A comparative study of griseofulvin-14C metabolism in the rat and rabbit.Biochem. Pharmacol.16: 2405–2411.
30.
30. Szabo G (1962). The number of eccrine sweat glands in human skin.Adv. Biol. Skin3: 1–9.
31.
31. Thomson ABR, Hotke CA, O'Brien BD, and Weinstein WM (1983). Intestinal uptake of fatty acids and cholesterol in four animal species and man: Role of unstirred water layer and bile salt micelle. Comp. Biochem. Physiol.75A: 221–232.
32.
32. Walker CH (1980). Species variations in some hepatic microsomal enzymes that metabolize xenobiotics. In: Progress in Drug Metabolism, Vol. 5, JW Bridges and LF Chasseaud (eds). John Wiley & Sons, New York, pp. 113–164.
33.
33. Wilkinson GR (1983). Plasma and tissue binding considerations in drug disposition.Drug Metab. Rev.14: 427–465.
34.
34. Yesair DW, Callahan M, Remington L, and Kensler CJ (1970). Role of the enterohepatic cycle of indomethacin on its metabolism, distribution in tissues and its excretion by rats, dogs and monkeys.Biochem. Pharmacol.19: 1579–1590.
