Coadministration of esomeprazole with fosamprenavir has no impact on steady-state plasma amprenavir pharmacokinetics.
OBJECTIVE
To evaluate the drug interaction between fosamprenavir (FPV) and esomeprazole (ESO) after repeated doses in healthy adults.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Shelton
Mark J
MJ
Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. Mark.J.Shelton@GSK.com
Ford
Susan L
SL
Borland
Julie
J
Lou
Yu
Y
Wire
Mary B
MB
Min
Sherene S
SS
Xue
Zhengyu G
ZG
Yuen
Geoffrey
G
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004338:Drug Combinations; D064098:Esomeprazole / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005663:Furans; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010755:Organophosphates / Q000008:administration & dosage* / Q000009:adverse effects; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D002219:Carbamates; D004338:Drug Combinations; D005663:Furans; D010755:Organophosphates; D013449:Sulfonamides; C095108:amprenavir; D064098:Esomeprazole; D019438:Ritonavir; C426859:fosamprenavir