title: Safety and pharmacokinetics of Bevirimat (PA-457), a novel inhibitor of human immunodeficiency virus maturation, in healthy volunteers.
abstract: Bevirimat (BVM; formerly known as PA-457) is a novel inhibitor of human immunodeficiency virus (HIV) maturation that is being developed for the treatment of HIV infection. The pharmacokinetics of this agent in healthy male volunteers were studied in a randomized, double-blind study in which the participants received single oral doses of placebo (n = 8) or escalating doses of BVM at 25, 50, 100, or 250 mg (n = 6 per dose); escalation was performed only after the pharmacokinetics and safety of the preceding dose had been evaluated. Plasma was collected over 480 h after dosing and urine was collected over 48 h after dosing for determination of the values of pharmacokinetic parameters. BVM was well absorbed after oral administration, with peak plasma concentrations being achieved 1 to 3 h after dosing. The half-life was 60 to 80 h. The exposure assessed by determination of the peak concentration and the area under the concentration-time curve was dose proportional. Single oral doses of BVM were well tolerated: there were no dose-limiting toxicities, and no serious adverse events were reported. These findings suggest that that BVM offers a favorable pharmacokinetic profile, with predictable pharmacokinetics following the oral administration of single doses. The long half-life of BVM may facilitate once-daily dosing.
authors.affiliation: Drug Development, Panacos Pharmaceuticals, 209 Perry Parkway, Suite 7, Gaithersburg, MD 20877, USA. dmartin@panacos.com
authors.forename: David E
authors.initials: DE
authors.lastname: Martin
authors.forename: Robert
authors.initials: R
authors.lastname: Blum
authors.forename: John
authors.initials: J
authors.lastname: Wilton
authors.forename: Judy
authors.initials: J
authors.lastname: Doto
authors.forename: Hal
authors.initials: H
authors.lastname: Galbraith
authors.forename: Gina L
authors.initials: GL
authors.lastname: Burgess
authors.forename: Philip C
authors.initials: PC
authors.lastname: Smith
authors.forename: Charles
authors.initials: C
authors.lastname: Ballow
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D013386:Succinates / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D014315:Triterpenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D053978:Pentacyclic Triterpenes
chemical_list: D019380:Anti-HIV Agents; D013386:Succinates; D014315:Triterpenes; C479935:bevirimat; D053978:Pentacyclic Triterpenes