HIV protease inhibitors: pharmacologic and metabolic distinctions

In the earlier era of nucleoside analogue antiretroviral therapy, considera tions of pharmacologic drug - drug interactions were only a small factor in choosing optimal therapies for patients with HIV infection. However, pharm acologic considerations are critical for selecting and managing the current multiple-drug antiretroviral regimens that include one or more HIV proteas e inhibitors (HPIs). Each of the available HPIs, both those that are licens ed and those still under investigation, has distinct pharmacokinetic and me tabolic properties that result in different dosing regimens and potential f or interactions with food and other drugs. Although drug interactions are u sually considered undesirable, some of the drug interactions between HPIs h ave beneficial effects on drug levels and total drug exposure. The non-nucl eoside reverse transcriptase inhibitors also interact with HPIs. This artic le briefly reviews pharmacokinetic and metabolic distinctions among the new er antiretroviral agents, especially HPIs, up to the end of 1997, including selected agents that are still under investigation. As current treatment g uidelines emphasize, HIV/AIDS patients typically receive several drugs; the refore, the potential for drug interactions, particularly those mediated by the P450 system in patients receiving HPIs or non-nucleoside reverse trans criptase inhibitors or both, must be appreciated by all physicians who care for patients with HIV disease. (C) 1999 Lippincott Williams & Wilkins.