The absorption, distribution, metabolism and elimination of bevirimat in rats.
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| Abstract |
Bevirimat is the first drug in the class of maturation inhibitors, which treat HIV infection by disrupting the activity of HIV protease enzyme with a mechanism of action distinct from that of conventional protease inhibitors. The absorption, distribution, metabolism and elimination characteristics of single intravenous (25 mg/kg) and oral (25 mg/kg and 600 mg/kg) doses of 14C-bevirimat were studied in male Sprague Dawley and Long Evans rats. Pharmacokinetic and mass-balance studies revealed that bevirimat was cleared rapidly (within 12-24 h) after dosing, although plasma radioactivity was quantifiable up to 168 h. Radioactive metabolites of bevirimat were responsible for approximately 60-80% of plasma radioactivity. Systemically available bevirimat was predominantly (97%) excreted via bile in the faeces, with <or=1% of the dose excreted renally. Less than 0.1% of the dose was excreted in expired air. Quantitative whole-body autoradiography detected high quantities of radioactivity in the bile and liver soon after intravenous dose administration, and evidence of biliary excretion present during the 8 h following oral dosing. Oral bioavailability for the 25 mg/kg dose of bevirimat was estimated at 22-24% by pharmacokinetic and mass-balance methods, with bioavailability decreasing disproportionately with increasing dose for the 600 mg/kg group.
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| Authors | Peter Bullock, Douglas Larsen, Randy Press, Tod Wehrman, David E Martin |
| Journal | Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 29 Issue 7 Pg. 396-405 (Oct 2008) ISSN: 0142-2782 [Print] England |
| PMID | 18615840 (Publication Type: Journal Article) |
| Copyright | Copyright (c) 2008 John Wiley & Sons, Ltd. |
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