Drug biotransformation pharmacokinetics

Loizou, G.D. and M.W.Anders. 1993. Gas-uptake pharmacokinetics and biotransformation of 1,1-dichloro-l-fluoroethane (HCFC-141b). Drug Metab. Disp. 21 634—713. 

Because most antidepressants require oxidative metabolism as a necessary step in their elimination, they can be the target of a pharmacokinetic drug-drug interaction, as well as the cause. The CYP enzymes mediating the biotransformation of the various antidepressants are also shown in Table 7-30. CYP 1A2 and 3A3/4 are induced by anticonvulsants such as barbiturates and carbamazepine. As expected, coadministration of these anticonvulsants has been shown to lower plasma levels of TCAs and would be predicted to have the same effect on nefazodone, sertraline, and venlafaxine. 

Introduction — This chapter summarizes significant contributions from the drug metabolism literature of the past year, with the objective of illustrating how pharmacokinetic and biotransformation information can assist in the discovery and development of new drugs. The format follows closely that of last year. The influence of structural alterations on drug disposition, metabolic events that lead to pharmacologically active or toxic substances, advances in novel or little studied biotransformations, and species differences in metabolism are discussed. 

Biotransformation in humans involves N-dealkylation and oxidation, but the isoenzymes involved in these reactions are as yet unidentified. As a consequence of its limited metabolic elimination, amisulpiride is unlikely to be involved in clinically relevant pharmacokinetic drug interactions. ... 

B. Testa, G. Cruciani, Structure-metabolism relations and the challenge of predicting biotransformation, in Pharmacokinetic Optimization in Drug Research, B. Testa, H. van de Water-beemd, G. Folkers, R. Guy (Eds.), WHey-VCH, Weinheim, New York, 2001, pp. 65-84. 

A second area of drug discovery and development in which enzyme reactions play a critical role is in the study of drug metabolism and pharmacokinetics. The elimination of xenobiotics, including drug molecules, from systemic circulation is driven by metabolic transformations that are entirely catalyzed by enzymes. Table 1.2 lists some of the enzyme-catalyzed transformations of xenobiotics that commonly contribute to drug molecule elimination. These biotransformation reactions... 

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