Conditions: Acquired Immunodeficiency Syndrome
Keywords: HIV ART HAART Pharmacokinetics Lopinavir/ritonavir Lower dose selection
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 22
Healthy volunteers: yes

Brief summary:
The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval, following administration to male and female HIV-negative healthy volunteers of:

1. Lopinavir/ritonavir 400/100 mg twice daily
2. Lopinavir/ritonavir 200/150 mg twice daily
3. Lopinavir/ritonavir 200/50 mg twice daily

Detailed description:
Data during the development of lopinavir/ritonavir showed that lower drug doses had similar efficacy to the standard dose of 400/100mg twice daily. Lower drug doses are also associated with limited toxicity and cost.

The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir following administration to male and female HIV-negative volunteers of 400/100mg, 200/150mg and 200/50mg lopinavir/ritonavir twice daily. Each dosing phase will last for 7 days and each phase will be separated by a 7-day wash-out period. Pharmacokinetic evaluations will be made over a 12-hour interval at the end of each dosing phase.

Healthy subjects as determined by their medical history and physical examinations will be eligible to participate in the study. HIV-positive subjects will not be recruited as there is a risk that HIV-resistant mutations will be selected by an experimentally reduced dose of lopinavir/ritonavir. There is no reason to presume that there is any meaningful difference in the metabolic processing of lopinavir/ritonavir between HIV-infected and HIV-uninfected people.

Arms:
arm 1: Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID)) arm 2: Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID) arm 3: Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)

Interventions: intervention 1: lopinavir/ritonavir
Intervention descriptions: intervention 1: Each participant received three sequential doses of lopinavir/ritonavir: 400/100 mg twice daily (2 heat-stable 200/50 mg tablets BID), 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID), and 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period.

Protocol document: