Interindividual variation in the enzymatic 15-keto-reduction of 13,14-dihydro-15-keto-prostaglandin E1 in human liver and in human erythrocytes

European Journal of Clinical Pharmacology
P Rady-PentekW Kalow

Abstract

The therapeutic response to PGE1 is highly variable, and a contribution by variable formation of its active tertiary metabolite PGE0 is in question. Hence, the objective of this study was to assess the person-to-person variation of the reduction of the inactive intermediate metabolite 15-KD PGE1 by human liver and human erythrocytes in forming the active metabolite PGE0. Source of enzyme was lysed erythrocytes from 29 donors, and a bank of 37 donor livers including specimens from 15 children. Tritium-labelled 13,14-dihydro-15-keto-prostaglandin E1 (15-KD PGE1) was used at low nanomolar concentrations and found to be converted almost exclusively to the more polar compound 13,14-dihydro-prostaglandin E1 (PGE0) by an NADPH-dependent carbonyl reductase. The identity of the product PGE0 was established by comparison of its chromatographic and mass spectral characteristics with authentic PGE0. Lysed erythrocytes had readily measurable enzymatic activity; differences between the preparations from 29 subjects were very small with only a twofold range of variation. In contrast to lysed erythrocytes, intact erythrocytes did not catalyse the reaction so that the erythrocyte activity should be medically immaterial. 15-KD PGE1 15-ketoreduct...Continue Reading

Citations

Feb 1, 2003·Current Therapeutic Research, Clinical and Experimental·Brookie M BestUNKNOWN Pediatric Pharmacology Research Unit Network
Jul 9, 2004·Drug Metabolism Reviews·M Jane Cox Rosemond, John S Walsh
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·M Strolin BenedettiE L Baltes
Jun 14, 2003·Fundamental & Clinical Pharmacology·M Strolin Benedetti, E L Baltes
Nov 6, 2013·Advanced Drug Delivery Reviews·Hannah K BatchelorSandra Klein
Nov 13, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sukhwinder S LakhmanJavier G Blanco

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