Potential role for P-glycoprotein in the nonproportional pharmacokinetics of UK-343,664 in man
- 1 January 2001
- journal article
- research article
- Published by Taylor & Francis in Xenobiotica
- Vol. 31 (8-9), 665-676
- https://doi.org/10.1080/00498250110052779
Abstract
1. UK-343,664 is a potent and specific PDE5 inhibitor. Following single oral doses to human volunteers, it exhibited non-proportional pharmacokinetics over the dose range 30-800mg. Over this 27-fold dose range, Cmax and AUCt increased 247- and 287-fold respectively. The half-life (4-6 h) was similar at all doses. No systemic exposure was quantifiable at doses 7.4 = 3.1) and as such is expected to be cleared mainly by metabolism. Based on studies with expressed human P450 enzymes it was concluded that the metabolism of UK-343,664 was predominantly mediated by CYP3A4. With a moderate KmKeywords
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