Effect of posaconazole on the pharmacokinetics of fosamprenavir and vice versa in healthy volunteers.
OBJECTIVE
To manage the interaction between fosamprenavir/ritonavir and posaconazole, we hypothesized that ritonavir can be replaced by posaconazole as an alternative booster of fosamprenavir with no significant influence on posaconazole pharmacokinetics.


METHODS
This was an open-label, randomized, three period, cross-over, single-centre trial in 24 healthy volunteers. All subjects received the following three treatments for 10 days, separated by washout periods of 17 days: posaconazole 400 mg twice daily; fosamprenavir/ritonavir 700/100 mg twice daily; posaconazole 400 mg twice daily with fosamprenavir 700 mg twice daily.


RESULTS
Twenty subjects completed the trial. Geometric mean ratios (GMR; +90% confidence interval) of posaconazole AUC and C(max) when taken with fosamprenavir versus posaconazole alone were 0.77 (0.68-0.87) and 0.79 (0.71-0.89), respectively. The GMRs of amprenavir AUC and C(max) when taken as fosamprenavir and posaconazole versus fosamprenavir/ritonavir were 0.35 (0.32-0.39) and 0.64 (0.55-0.76), respectively. No serious adverse events were reported during the trial.


CONCLUSIONS
Unboosted fosamprenavir should not be used concomitantly with posaconazole.
Brüggemann
Roger J M
RJ
Radboud University Nijmegen Medical Centre, Department of Clinical Pharmacy, Nijmegen, The Netherlands. r.bruggemann@akf.umcn.nl
van Luin
Matthijs
M
Colbers
Engelina P H
EP
van den Dungen
Myrthe W
MW
Pharo
Cristina
C
Schouwenberg
Bas J J W
BJ
Burger
David M
DM
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D005663:Furans; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D019380:Anti-HIV Agents; D000935:Antifungal Agents; D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D013449:Sulfonamides; D014230:Triazoles; C101425:posaconazole; C426859:fosamprenavir