Abstract
The literature was reviewed to obtain data from 11 mammalian species on liver weight, hepatic blood flow, and antipyrine intrinsic clearance. It was demonstrated that liver weight and hepatic blood flow in all species could be readily related to body weight by a simple equation. Additionally, hepatic blood flow in all species was directly proportional to liver weight. With the exception of man, antipyrine intrinsic clearance was also directly proportional to liver weight. Man's intrinsic clearance was approximately one-seventh of that which would be predicted from other species. Data on benzodiazepines and phenytoin showed a similar pattern.
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References
L. B. Mellett. Comparative drug metabolism.Prog. Drug Res. 13:136–169 (1969).
M. Weib, W. Sziegoleit, and W. Förster. Dependence of pharmacokinetic parameters on the body weight.Int. J. Clin. Pharmacol. 15:572–575 (1977).
K. B. Bishoff, R. L. Dedrick, D. S. Zaharko, and J. A. Longstreth. Methotrexate pharmacokinetics.J. Pharm. Sci. 60:1128–1133 (1971).
U. Klotz, K.-H. Antonin, and P. R. Bieck. Pharmacokinetics and plasma binding of diazepam in man, dog, rabbit, guinea pig and rat.J. Pharmacol. Exp. Ther. 199:67–73 (1976).
B. B. Brodie. Of mice, microsomes and man.Pharmacologist 6:12–26 (1964).
R. H. Wickramasinghe and C. A. Villee. Early role during chemical evolution for cytochrome P450in oxygen detoxification.Nature 256:509–511 (1975).
R. H. Wickramasinghe and C. A. Villee. Possible similar role of cytochrome P450 in primordial evolution of species and in chemical carcinogenesis.Persp. Biol. Med. 19:473–475 (1976).
J. R. Mitchell and D. J. Jollows. Metabolic activation of drugs to toxic substances.Gastroenterology 68:392–411 (1975).
G. R. Wilkinson and D. G. Shand. A physiological approach to hepatic drug clearance.Clin. Pharmacol. Ther. 18:377–390 (1975).
M. Rowland, T. F. Blaschke, P. J. Meffin, and R. L. Williams. Pharmacokinetics in disease states modifying hepatic and metabolic function. In L. Z. Benet (ed.),The Effect of Disease States on Drug Pharmacokinetics, Am. Pharm. Assoc., Acad. Pharm. Sci., Washington, D.C., 1976, Chap. 4, pp. 53–75.
E. F. Adolph. Quantitative relations in the physiological constitutions of mammals.Science 109:579–585 (1949).
B. B. Brodie and J. Axelrod. The fate of antipyrine in man.J. Pharmacol. Exp. Ther. 98:97–104 (1950).
H. Yoshimura, H. Shimeno, and H. Tsukamoto. Metabolism of drugs. LIX. A new metabolite of antipyrine.Biochem. Pharmacol. 17:1511–1516 (1968).
H. Yoshimura, H. Shimeno, and H. Tsukamoto. Metabolism of drugs. LXX. Further study on antipyrine metabolism.Chem. Pharm. Bull. 19:41–45 (1971).
J. D. Baty and D. A. Price Evans. Norphenazone, a new metabolite of phenazone in human urine.J. Pharm. Pharmacol. 25:83–84 (1973).
O. M. Bakke, M. Bending, J. Aabakke, and D. S. Davies.14C-Antipyrine as a model compound in the study of drug oxidation and enzyme induction in individual surviving rats.Acta Pharmacol. Toxicol. 35:91–97 (1974).
M. Stafford, G. K. Mann, R. N. Stillwell, and M. G. Horning. Metabolism of antipyrine by the epoxide-diol pathway in the rat, guinea pig and human.Res. Commun. Chem. Pathol. Pharmacol. 8:593–606 (1974).
E. Mayr.Populations, Species, and Evolution, Chap. 9: Storage and protection of genetic variation, Belknap Press, Cambridge, Mass., 1970, pp. 129–161.
Data on file. Hoffmann-La Roche, Nutley, N.J.
R. W. Lucek and C. B. Coutinho. The role of substituents in the hydrophobic binding of the 1,4-benzodiazepines by human plasma proteins.Mol. Pharmacol. 12:612–619 (1976).
S. A. Kaplan, M. L. Jack, R. E. Weinfeld, W. Glover, L. Weissman, and S. Cotler. Biopharmaceutical and clinical pharmacokinetic profile of bromazepam.J. Pharmacokin. Biopharm. 4:1–16 (1976).
I. Bekersky, A. C. Maggio, V. Mattaliano, Jr., H. G. Boxenbaum, D. E. Maynard, P. D. Cohn, and S. A. Kaplan. Influence of phenobarbital on the disposition of clonazepam and antipyrine in the dog.J. Pharmacokin. Biopharm. 5:507–512 (1977).
A. Berlin and H. Dahlström. Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration.Eur. J. Clin. Pharmacol. 9:155–159 (1975).
H. G. Boxenbaum, K. A. Geitner, M. L. Jack, W. R. Dixon, H. E. Spiegel, J. Symington, R. Christian, J. D. Moore, L. Weissman, and S. A. Kaplan. Pharmacokinetic and biopharmaceutic profile of chlordiazepoxide HC1 in healthy subjects: Single-dose studies by the intravenous, intramuscular, and oral routes.J. Pharmacokin. Biopharm. 5:3–23 (1977).
S. A. Kaplan, M. Lewis, M. A. Schwartz, E. Postma, S. Cotler, C. W. Abruzzo, T. L. Lee, and R. E. Weinfeld. Pharmacokinetic model for chlordiazepoxide-HCl in the dog.J. Pharm. Sci. 59:1569–1574 (1970).
M. A. Schwartz, E. Postma, S. J. Kolis, and A. S. Leon. Metabolites of bromazepam, a benzodiazepine, in the human, dog, rat, and mouse.J. Pharm. Sci. 62:1776–1779 (1973).
H. Sawada and A. Hara. Studies on metabolism of bromazepam. V. Identification of new urinary metabolites and their excretion pattern in various animal species.Yakugaku Zasshi. 95:430–438 (1975).
S. A. Kaplan, K. Alexander, M. L. Jack, C. V. Puglisi, J. A. F. deSilva, T. L. Lee, and R. E. Weinfeld. Pharmacokinetic profiles of clonazepam in dog and humans and flunitrazepam in dog.J. Pharm. Sci. 63:527–532 (1974).
T. F. Blaschke, P. J. Meffin, K. L. Melmon, and M. Rowland. Influence of acute viral hepatitis on phenytoin kinetics and protein binding.Clin. Pharmacol. Ther. 17:685–691 (1975).
P. G. Dayton, S. A. Cucinell, M. Weiss, and J. M. Perel. Dose-dependence of drug plasma level decline in dogs.J. Pharmacol. Exp. Ther. 158:305–316 (1967).
Y. Saitoh, K. Nishihara, F. Nakagawa, and T. Suzuki. Improved microdetermination of diphenylhydantoin in blood by UV spectrophotometry.J. Pharm. Sci. 62:206–210 (1973).
J. D. Baggot and L. E. Davis. Comparative study of plasma protein binding of diphenylhydantoin.Comp. Gen. Pharmacol. 4:399–404 (1973).
A. Yacobi and G. Levy. Intraindividual relationships between serum protein binding of drugs in normal human subjects, patients with impaired renal function, and rats.J. Pharm. Sci. 66:1285–1288 (1977).
G. Levy and J. J. Ashley. Effect of an inhibitor of glucuronide formation on elimination kinetics of diphenylhydantoin in rats.J. Pharm. Sci. 62:161–162 (1973).
D. W. Shoeman, R. E. Kauffman, D. L. Azarnoff, and B. M. Boulos. Placental transfer of diphenylhydantoin in the goat.Biochem. Pharmacol. 21:1237–1243 (1972).
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Boxenbaum, H. Interspecies variation in liver weight, hepatic blood flow, and antipyrine intrinsic clearance: Extrapolation of data to benzodiazepines and phenytoin. Journal of Pharmacokinetics and Biopharmaceutics 8, 165–176 (1980). https://doi.org/10.1007/BF01065191
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DOI: https://doi.org/10.1007/BF01065191