Six-Week Randomized Controlled Trial To Compare the Tolerabilities, Pharmacokinetics, and Antiviral Activities of GW433908 and Amprenavir in Human Immunodeficiency Virus Type 1-Infected Patients
Creators: name: Stellbrink, H.-J.
name: Raffi, F.
name: Naderer, O. J.
name: Teofilo, E.
name: Eron, J.
name: Wire, M. B.
name: Yeo, J.
name: Wood, R.
name: Arasteh, K.
name: Pollard, R. B.
name: Millard, J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2004

description: This study compared the plasma amprenavir pharmacokinetics of the human immunodeficiency virus (HIV) protease inhibitors amprenavir (Agenerase) 1,200 mg twice daily (BID) and the amprenavir prodrug {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908, a formulation that substantially reduces the number of tablets per dose compared with amprenavir, at doses of 1,395 mg and 1,860 mg BID, in combination with abacavir 300 mg BID and lamivudine 150 mg BID in patients with HIV infection. Overall, 78 patients received study treatment. Compared with amprenavir 1,200 mg BID, both {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908 1,395 mg BID and {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908 1,860 mg BID delivered equivalent steady-state (ss) values for area under the plasma amprenavir concentration-time curve (AUC) at the end of a dosing interval (τ), lower maximum plasma amprenavir concentrations (30% lower), and higher plasma amprenavir concentrations at the end of a dosing interval (28% higher for {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908 1,395 mg BID and 46% higher for {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908 1,860 mg BID). Time-variant plasma amprenavir pharmacokinetics were observed with reductions in plasma amprenavir exposure over the first 4 weeks of dosing; the decrease in plasma amprenavir AUCτ,ss versus the AUC from 0 h to ∞ was 27% for GW43308 1,395 mg, 45% for {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908 1,860 mg, and 23% for amprenavir 1,200 mg. All three regimens reduced plasma HIV-1 RNA (∼2 log10 copies/ml) and increased CD4+ cell counts (∼100 cells/mm3) over the initial 28 days. Adverse event profiles were consistent with those previously reported for amprenavir. Although not statistically tested, the {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908 groups appeared to have fewer gastrointestinal symptoms. In conclusion, the protease inhibitor {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908 delivered comparable plasma amprenavir concentrations to those delivered by amprenavir 1,200 mg BID. {"type":"entrez-nucleotide","attrs":{"text":"GW433908","term_id":"315882026","term_text":"GW433908"}}GW433908, in combination with abacavir and lamivudine, demonstrated potent antiviral activity and was generally well tolerated over a 4-week period.