Biotransformations : a survey of the biotransformations of by D R Hawkins

By D R Hawkins

Now in its 7th impressive quantity, Biotransformations has develop into tested as a different and demanding resource for these fascinated by the invention and improvement of latest compounds. It extensively covers the medical literature for the interval 1987 to 1994. The sequence offers a whole survey of the biotransformations, in vertebrates, of the next: prescription drugs; agrochemicals; foodstuff ingredients; environmental chemical substances; commercial chemical compounds. Biotransformations presents a prepared method of having access to details at the recognized pathways for the biotransformation of structurally-related compounds. Key useful teams supply an index-related technique for retrieving info on compounds of curiosity. one more index permits the retrieval of examples of particular biochemical reactions that may have wider software. each one quantity corresponds approximately with the medical literature released in the course of a calendar yr. every one quantity incorporates a overview bankruptcy which discusses examples of novel biotransformations, species transformations, stereochemical facets and mechanisms of toxicity linked to particular biotransformations. learn more... summary: Now in its 7th amazing quantity, Biotransformations has turn into confirmed as a distinct and significant resource for these keen on the invention and improvement of recent compounds. It generally covers the clinical literature for the interval 1987 to 1994. The sequence offers a whole survey of the biotransformations, in vertebrates, of the subsequent: prescription drugs; agrochemicals; nutrition ingredients; environmental chemical substances; business chemical substances. Biotransformations offers a prepared manner of gaining access to details at the identified pathways for the biotransformation of structurally-related compounds. Key practical teams supply an index-related strategy for retrieving details on compounds of curiosity. a different index permits the retrieval of examples of particular biochemical reactions which can have wider software. each one quantity corresponds approximately with the clinical literature released in the course of a calendar yr. each one quantity encompasses a evaluation bankruptcy which discusses examples of novel biotransformations, species adjustments, stereochemical points and mechanisms of toxicity linked to particular biotransformations

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The formation of thiol conjugates of these acids has been compared to evaluate whether the acid metabolite of valproic acid might be associated with its hepatotoxicity (p. 83). Three major metabolites of (79) in rat bile were identified as isomeric glutathione conjugates of (80). By contrast no thiol conjugates of the keto-acid (81) were identified after administration of the valproic acid metabolite. The only metabolites detected were the known conjugates of the dienoic acid (82). There are 10 therefore basic differences in the metabolism of these two structurally related acids.

Two major novel metabolites of the calcium antagonist SM-6586 (31) have been isolated from the bile of rats after oral doses (p. 259). It is of interest that one metabolite (32) retained the dihydropyridine structure and the intact methyl ester function. This metabolite could be formed by oxidative N-dealkylation of the side-chain and subsequent decarboxylation. The second metabolite (33) was formed by loss of the side-chain and cleavage of the oxadiazole ring to give an unusual cyanamide function.

The major component in plasma was the R-enantiomer with the AUC being more than 70-fold higher than that for the S-enantiomer. A major component in urine was a glucuronide of the parent drug which was virtually all derived from the S-enantiomer. This is consistent with the rapid clearance of this enantiomer from plasma and presumably associated with stereoselective glucuronidation. OH N C - @ l H C O I$ H I S O O F The stereospecific aspects of the metabolism of the racemic drug stiripentol have provided a fascinating example of the importance of understanding the disposition of individual enantiomers in a racemic drug (p.

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