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Xenobiotica
the fate of foreign compounds in biological systems
Volume 18, 1988 - Issue 2
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Original Article

Metabolism of alfentanil by isolated hepatocytes of rat and dog

, , , , , , & show all
Pages 183-197 | Received 18 Jan 1987, Published online: 30 Sep 2009
 

Abstract

1. The biotransformation of 3H-alfentanil was studied using suspension cultures of isolated hepatocytes of male and female rats and of dogs.

2. In hepatocytes of the male rat, alfentanil was readily metabolized, following linear Michaelis-Menten kinetics over the concentration range 5—400μM. The metabolism was strongly inhibited by the cytochrome P-450 inhibitors metyrapone, α-naphthoflavone and piperonyl butoxide.

3. The major metabolites of alfentanil, which were formed in suspension cultures of male rat hepatocytes, were identified by h.p.l.c. co-chromatography and by mass spec-trometry and included N-[4-(hydroxymethyl)-4-piperidinyl]-N-phenylpropanamide. N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide or noralfentanil and N-[1-[2-(4-ethyl-4,5-dihydro-5-oxo-1-H-tetrazol-1-yl)ethyl]-4-(hydroxymethyl)-4-piperidinyl]-N-phenylpropanamide or desmethylalfentanil.

4. The major in-vitro metabolic pathways of alfentanil in hepatocytes of the three sources were oxidative N-dealkylation at the piperidine nitrogen and oxidative O-demethylation at the methoxymethyl moiety.

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