Clinical Pharmacologic Considerations for HIV-1 Protease Inhibitors.
Many data associate low protease inhibitor plasma concentrations with suboptimal virologic responses, whereas relatively few data associate high plasma concentrations with increased likelihood of toxicity. Knowledge of relationships between concentrations and virologic response is important because significant variability in plasma concentrations exists among HIV-infected persons. Unfortunately, a prospectively confirmed therapeutic range that reduces the risk of virologic failure has not been established for the protease inhibitors. Recent investigations have identified a relationship between the measured minimum plasma concentration, the in vitro susceptibility of the subject's virus, and virologic outcome. However, differences in virologic response may further depend on other pharmacologic factors such as protein binding, intracellular kinetics, expression of drug transporters, and drug synergies or antagonisms. In the future, dosing strategies that accommodate the variability in both pharmacokinetics and pharmacodynamics may improve virologic outcomes. In summary, clinical pharmacologic considerations for protease inhibitors can be used to promote their optimal use.
Anderson
Peter L.
PL
University of Minnesota, Department of Experimental and Clinical Pharmacology, 7-151 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA. fletc001@tc.umn.ed u
Fletcher
Courtney V.
CV