Assessment of the extent to exogenous prostaglandin I2 is converted to 6-keto-prostaglandin E1 in human subjects.
6-Keto-prostaglandin (PG) E1 has been suggested as a possible active metabolite of PGI2. The objective of this study was to evaluate whether 6-keto-PGE1 might mediate the biological responses of exogenous PGI2 in man. Toward this end, a novel gas chromatographic-mass spectrometric assay for 6-keto-PGE1, was developed. Selective ion monitor traces from human plasma detected levels that were at the lower limit of sensitivity for this assay and positive mass spectral identification was not possible. An infusion of PGI2 (8 ng/kg/min) which caused systemic hemodynamic changes did not alter plasma levels of 6-keto-PGE1. We conclude that exogenous PGI2 is not converted to an appreciable extent to 6-keto-PGE1 in man and, therefore, 6-keto-PGE1 biosynthesis is unlikely to be responsible for the biological effects of infused PGI2.
D000328:Adult; D000527:Alprostadil / Q000031:analogs & derivatives*; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism
D011453:Prostaglandins; D011458:Prostaglandins E; C022950:6-ketoprostaglandin E1; D011464:Epoprostenol; D000527:Alprostadil