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Influence of probenecid and paracetamol (acetaminophen) on zidovudine glucuronidation in human liver in vitro

✍ Scribed by F. Kamali; M. D. Rawlins

Publisher: John Wiley and Sons
Year: 1992
Tongue: English
Weight: 347 KB
Volume: 13
Category: Article
ISSN: 0142-2782
DOI: 10.1002/bdd.2510130603

No coin nor oath required. For personal study only.

✦ Synopsis

The effects of probenecid and paracetamol on zidovudine glucuronidation were investigated, in vitro, using human liver microsomal preparations. The presence of probenecid in the incubation medium significantly reduced the maximum reaction velocity for zidovudine glucuronide formation by more than 60 per cent, and the K, was reduced by 47 per cent, suggesting an uncompetitive inhibition of zidovudine glucuronidation. In contrast, paracetamol had no significant effect on zidovudine glucuronidation. The maximum reaction velocity for zidovudine glucuronide formation and the K, were unchanged when paracetamol (5 mM) was present in the incubation medium. The effects of probenecid and paracetamol on zidovudine metabolism in vitro correlates closely with those observed in vivo. The in vitro system of human liver microsomes may have a useful role in predicting the possible interaction of other drugs with zidovudine metabolism.

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