Shelton Mark J, Ford Susan L, Borland Julie, Lou Yu, Wire Mary B, Min Sherene S, Xue Zhengyu G, Yuen Geoffrey
Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
J Acquir Immune Defic Syndr. 2006 May;42(1):61-7. doi: 10.1097/01.qai.0000219770.97303.43.
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.
评估健康成年人多次服用福沙那韦（FPV）和埃索美拉唑（ESO）后的药物相互作用。
受试者每天一次服用20mg ESO，共7天，随后在第1组和第2组中，分别在接下来的14天里每天一次服用20mg ESO加每天两次服用1400mg FPV，或每天一次服用20mg ESO加每天两次服用700mg FPV加100mg利托那韦（RTV）。经过21至28天的洗脱期后，受试者在第1组中每天两次服用1400mg FPV，共14天，或在第2组中每天两次服用700mg FPV加100mg RTV，共14天。在每种治疗的最后一天进行药代动力学采样。
每天一次服用20mg ESO与每天两次服用1400mg FPV或每天两次服用700mg FPV加100mg RTV同时给药，对安普那韦稳态药代动力学没有影响。对血浆ESO暴露的唯一影响是，在每天一次服用20mg ESO与每天两次服用1400mg FPV同时给药后，给药间隔期内血浆浓度-时间曲线下面积（tau[AUC0-tau]）增加了55%。
每天两次服用1400mg FPV或每天两次服用700mg FPV加100mg RTV可与ESO同时给药，无需调整剂量。然而，目前尚不清楚质子泵抑制剂（PPI）错开给药对血浆安普那韦暴露的影响。
