The purpose of this study is to determine the influence of posaconazole on unboosted fosamprenavir pharmacokinetics, and vice versa, in healthy volunteers.A second objective is to determine the safety of combined use of fosamprenavir with posaconazole in healthy volunteers.
Infections with fungi and yeast frequently occur in patients infected with the human immunodeficiency virus type 1 (HIV-1). Fosamprenavir is a PI that is used to treat HIV-infection in combination with ritonavir. Once hydrolyzed to amprenavir, this substance is a substrate for CYP3A4. Ritonavir is an extremely potent inhibitor of CYP3A4 and serves as a booster of the pharmacokinetics of amprenavir. Posaconazole is a very potent CYP3A4 inhibitor and therefore might enhance amprenavir pharmacokinetics in a similar way as ritonavir. The current study is designed to test this hypothesis. When there is an indication for antifungal therapy in an HIV-infected patient, temporal replacement of ritonavir by posaconazole would be an attractive option for combined treatment of HIV and fungal infection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Posaconazole oral solution 40mg/mL; 400mg BID treatment for 10 days, including dose escalation
fosamprenavir tablet 700mg; 1 tablet BID for 10 days
Ritonavir 100mg capsule; 1 capsule BID for 10 days
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands
Plasma concentrations of amprenavir and posaconazole
Time frame: predose and at 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours after dosing on Study Days 10, 38 and 66. Predose on study days 1, 3, 5, 8, 29, 31, 33, 36, 57, 59, 61, and 64.
Adverse events (safety) due to concomitant use of fosamprenavir and posaconazole
Time frame: period of interaction treatment
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