Differences in the pharmacokinetics of protease inhibitors between healthy volunteers and HIV-infected persons.
OBJECTIVE
Pharmacokinetic and drug-drug interaction studies are conducted in both healthy volunteers and the target population (HIV-infected patients), but there is little discussion of the potential for differences in drug disposition between the two groups. It is important to recognize that the pharmacokinetics of drugs may be altered in HIV-infected persons as compared with healthy individuals. The aim of this review is to highlight some of the important differences in drug handling between healthy volunteers and HIV-infected individuals, focusing on protease inhibitors.


RESULTS
Studies aimed at characterizing disparities in pharmacokinetics between healthy volunteers and HIV patients are lacking. Data suggest that concentrations of some protease inhibitors are lower in HIV patients than in HIV-negative volunteers (atazanavir and tipranavir), but generally comparisons are made across studies and study centres, and so multiple variables, such as differences in food and study design, can influence findings. We have conducted an 'in-house' analysis, comparing atazanavir, lopinavir and saquinavir between HIV-infected patients and healthy volunteers enrolled in the same study centre with similar study designs.


CONCLUSIONS
For atazanavir the current data are quite convincing that concentrations are lower in HIV-infected patients than in healthy individuals, but for others it is not so clear. The 'in-house' analyses for atazanavir, lopinavir and saquinavir attempted to address some of the difficulties with cross-study comparisons, but it should be noted that subject numbers were small. Physiological changes resulting from HIV disease can influence drug pharmacokinetics and the underlying mechanisms remain to be elucidated.
Dickinson
Laura
L
Department of Pharmacology & Therapeutics, University of Liverpool, Liverpool L69 3GF, UK. laurad@liv.ac.uk
Khoo
Saye
S
Back
David
D