Changes in the enzymatic activities of beagle liver during maturation as assessed both in vitro and in vivo

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
E TanakaS Misawa

Abstract

1. We have examined changes in caffeine and trimethadione (TMO) metabolism in vivo, agents which are used as probe drugs. In this study the total body clearance (Cl) of caffeine and TMO was low 1 week after birth (week 1), increased rapidly from week 3, peaked and then decreased gradually until reaching the level for the mature, adult dog. The elimination half-life (t1/2) of caffeine and TMO was prolonged during week 1; however, it then gradually became shorter. Gradually it became longer and reached the level for the adult dog. The apparent volume of distribution (Vd) of caffeine did not change throughout the study. However, the Vd of TMO was only high during week 1. 2. The in vitro changes in a variety of typical substrates for seven different cytochrome P450 (CYP) isozymes were examined. In this study three different patterns of metabolism can be identified: (1) activity is low immediately after birth, increases, peaks and then decreases to the adult dog level (p-nitroanisole; CYP1A1, caffeine; CYP1A2, benzphetamine; CYP3A/2B(?), aniline; 2E1 and TMO; CYP2C9/2E1/3A4); (2) activity generally increases rapidly soon after birth, continues to increase, peaks and then gradually decreases to the adult level (phenytoin; CYP2C9); an...Continue Reading

References

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Citations

Jun 9, 2001·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·K WaltonA G Renwick
Sep 12, 2002·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Zoheir A Damanhouri
Jun 8, 2011·Future Medicinal Chemistry·Leposava Antonovic, Marilyn Martinez
Mar 15, 2003·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M J GrahamM S Lennard
Aug 6, 2011·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Peter MansellGregg D Cappon
Oct 2, 2014·Journal of Veterinary Pharmacology and Therapeutics·M D Pairis-GarciaJ F Coetzee
Apr 18, 2008·European Journal of Pharmacology·Johanna Fink-Gremmels
Jun 25, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Masashi MiseSetsuko Komuro
Dec 17, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Beth Miskimins MillsCharles W Locuson

Related Concepts

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