Pharmacokinetic Study of Posaconazole Boosted Fosamprenavir

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.

Inclusion criteria

• Subject is at least 18 and not older than 55 years of age on the day of the first dosing.
• Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing.
• Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to the first dose.
• Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.

Exclusion criteria

• Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
• Positive HIV test.
• Positive hepatitis B or C test.
• Pregnant female (as confirmed by an HCG test performed less than 4 weeks before the first dose) or breast-feeding female.
• Therapy with any drug (for two weeks preceding dosing), except for paracetamol.
• Subjects with an ECG with QTc interval greater than 450 ms for men, and greater than 470 ms for women at screening.
• Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• History of or current abuse of drugs, alcohol or solvents.
• Inability to understand the nature and extent of the trial and the procedures required.
• Participation in a drug trial within 60 days prior to the first dose.
• Donation of blood within 60 days prior to the first dose.
• Febrile illness within 3 days before the first dose