s-1743 and fosamprenavir

The effects of proton pump inhibitors on the pharmacokinetics of atazanavir and amprenavir (administered as fosamprenavir) were rigorously evaluated in healthy volunteers in two studies, but formal studies in persons infected with human immunodeficiency virus (HIV) are lacking. We describe a 65-year-old man with HIV who underwent a 12-hour intensive pharmacokinetic study while receiving esomeprazole with atazanavir-ritonavir and subsequently, an 8-hour study while receiving esomeprazole with fosamprenavir-ritonavir. Consistent with the data in healthy volunteers, a major interaction between esomeprazole and atazanavir-ritonavir was observed in this patient-marked reductions in atazanavir trough plasma concentration and in the area under the concentration-time curve from 0-24 hours-whereas an interaction between esomeprazole and fosamprenavir-ritonavir was not apparent in this patient.

Topics: Aged; Anti-HIV Agents; Anti-Ulcer Agents; Atazanavir Sulfate; Carbamates; Drug Interactions; Esomeprazole; Furans; HIV Infections; HIV Protease Inhibitors; Humans; Male; Oligopeptides; Organophosphates; Prospective Studies; Proton Pump Inhibitors; Pyridines; Sulfonamides

To evaluate the drug interaction between fosamprenavir (FPV) and esomeprazole (ESO) after repeated doses in healthy adults.. Subjects received ESO 20 mg once daily (qd) for 7 days followed by either ESO 20 mg qd + FPV 1400 mg twice daily (bid) or ESO 20 mg qd + FPV 700 mg bid + ritonavir (RTV) 100 mg bid for 14 days in arms 1 and 2, respectively. After a 21- to 28-day washout, subjects received either FPV 1400 mg bid for 14 days (arm 1) or FPV 700 mg bid + RTV 100 mg bid for 14 days (arm 2). Pharmacokinetic sampling was conducted on the last day of each treatment.. Simultaneous coadministration of ESO 20 mg qd with either FPV 1400 mg bid or FPV 700 mg bid + RTV 100 mg bid had no effect on steady-state amprenavir pharmacokinetics. The only effect on plasma ESO exposure was a 55% increase in area under the plasma concentration-time curve during a dosing interval, tau[AUC0-tau], after coadministration of ESO 20 mg qd with FPV 1400 mg bid.. FPV 1400 mg bid or FPV 700 mg bid + RTV 100 mg bid may be coadministered simultaneously with ESO without dose adjustment. However, the impact of staggered administration of proton pump inhibitors (PPI) on plasma amprenavir exposure is unknown at present.

Topics: Administration, Oral; Adolescent; Adult; Carbamates; Diarrhea; Drug Administration Schedule; Drug Combinations; Esomeprazole; Female; Furans; Headache; Humans; Male; Middle Aged; Nausea; Organophosphates; Ritonavir; Sulfonamides

A study suggested that the two drugs might be used together, without lowering the blood level of Lexiva. But the timing of the doses may be critical.

Topics: Anti-HIV Agents; Carbamates; Drug Administration Schedule; Drug Interactions; Esomeprazole; Furans; HIV Infections; Humans; Organophosphates; Sulfonamides