Metabolism extrahepatic

Krishna, D. R. Klotz, U. (1994). Extrahepatic metabolism of drugs in humans. Clin. Pharma-cokinet., 26, 144—60. 

T. E. Gram, The metabolism of xenobiotics by the mammalian lung, in Extrahepatic Metabolism of Drugs and Other Foreign Compounds (T. E. Gram, Ed.), S.P. Medical and Scientific Books, New York, 1980, pp. 159-209. 

Gram TE, ed. Extrahepatic Metabolism of Drugs and Other Foreign Compounds. Jamaica, New York Spectrum Publications, 1980. 

James, M.O., et al. Hepatic and extrahepatic metabolism in vitro of an epoxide (8- 0-styrene oxide) in the rabbit. 

Veroli P, O Kelly B, Bertrand F, et al. Extrahepatic metabolism of propofol in man during the anhepatic phase of orthotopic liver transplantation. Br J Anaesth 1992 68(2) 183-186. 

Fumes B, Schlenk D. Extrahepatic metabolism of carbamate and organophosphate thioether compounds by the flavin-containing monooxygenase and cytochrome P450 systems. Drug Metab Dispos 2005 33 214—218. 

Heinrichs, W.L., and M.R. Juchau. Extrahepatic drug metabolism The gonads, pp. 319-332. In T. Gram, Ed. Extrahepatic Metabolism of Drugs and Other Foreign Compounds. New York Spectrum, 1980. 

Pioglitazone and rosiglitazone are well absorbed orally and highly protein-bound. Multiple CYP isoforms are involved in their hepatic and, to a lesser degree, extrahepatic metabolism. Pioglitazone may be a weak inducer of CYP enzymes. 

Induction of extrahepatic mdoleamine dioxygenase (which catalyzes the same reaction as tryptophan dioxygenase, albeit by a different mechanism) by bacterial lipopolysaccharides and mterferon-y may result in the production of relatively large amounts of kynurenine and hydroxykynurenine in tissues that lack the enzymes for onward metabolism. Kidney has kynurenine transaminase activity, and therefore extrahepatic metabolism of tryptophan may result in significant excretion of kynurenic and xanthurenic acids, even when vitamin Bg nutrition is adequate. 

The liver has been the focus of most drug metabolism studies. While there is extrahepatic metabolism of some drugS/ which may be extensive in some caseS/ the liver is generally considered the dominant organ in drug metabolism. Since liver tissue can be obtained from most specieS/ including humanS/ in vitro study of hepatic metabolism has been... 

Similar predictions of in vivo intrinsic clearance in the human from in vitro data have been produced by Ito et al. (20). The results are shown in Figure 30.12. The liver blood flow of about 1 niL/min g places the intrinsic clearances in perspective. These correlations show considerably more variability than do those for the rat. This reflects both methodologic difficulties and probably a large variability of enzyme activities within the human population. Also there seems to be a systematic underprediction for low-clearance drugs. This may reflect difficulties in measuring these low rates in vitro and/or extrahepatic metabolism. 

TCE is extensively metabolized (40-75% of the retained dose) in humans to trichloroethanol, glucuronides, and trichloroacetic acid (TCA). Saturation of metabolism has not been demonstrated in humans up to an exposure concentration of 300 ppm. Mathematical models predict, however, that saturation of metabolism is possible at TCE concentrations previously used for anesthesia (i.e., 2000 ppm). Although the liver is the primary site of TCE metabolism in animals, there is evidence for extrahepatic metabolism of trichloroethylene in the kidneys and lungs. 

Three benzodiazepines undergo extrahepatic metabolism and do not form active metabolites Oxazepam, Temazepam, Lorazepam. 

GRAM, T.E. (editor) (1980) Extrahepatic Metabolism of Drugs and Other Foreign Compounds (Jamaica, New York Spectrum Publications). (This text contains chapters on various aspects of drug metabolism, both phase 1 and phase 2.)... 

A series of reviews describing nicotine metabolism has recently appeared [2], Specific topics covered include the biosynthesis and metabolism of nicotine and related alkaloids [3], an overview of mammalian nicotine metabolism [4], the role of cytochrome P450 in nicotine metabolism [5], nicotine metabolism beyond cotinine [6], N-oxidation, A -methylation, and N-conjugation reactions of nicotine [7], extrahepatic metabolism of nicotine and related compounds [8], metabolism of the minor tobacco alkaloids [9], analysis and levels of nicotine and metabolites in body fluids [10], kinetics of nicotine and its metabolites in animals [11], pharmacokinetics of (S)-nicotine and metabolites in humans [12], and sources of inter-individual variation in nicotine pharmacokinetics [13]. Another recent review described variables which affect nicotine metabolism [14]. Several compilations of studies or reviews on the tobacco-specific A-nitrosamines are available [15-18]... 

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