Pharmacokinetics and pharmacodynamics of drug interactions involving HIV-1 protease inhibitors
Jackson A., Taylor S., Boffito M.
Therapeutic agents used to inhibit the HIV-1 protease are integral to the effective suppression of HIV virus replication by use of synergistic combination therapy. This is inherently dependent on the achievement of effective plasma concentrations of the drug in its active form, and sustaining such levels for the duration of a dosing interval without exceeding thresholds of toxicity. The issues determining the absorption, biotransformation, distribution to and activity at the intended site, and elimination, are myriad and complex. Studies at molecular, cell, and tissue levels are useful for predicting the possible fate of these agents at in vivo, but the wide interindividual variability shown in whole-body pharmacokinetic studies is illustrative of the difficulty in making general statements rather than more guarded recommendations. This paper summarizes the current state of understanding of the major interactions between protease inhibitors themselves and other important commonly used agents in the management of HIV disease, based on data from clinical pharmacokinetic studies.