Indications
Nevirapine is primarily indicated for use in conjunction with other antiretroviral agents in the sustained management of HIV-1 infection. This combination therapy approach is vital, as it helps enhance efficacy and prevent the development of resistance. Nevirapine is particularly recommended after the patient's immune function has declined and opportunistic infections have emerged.
Pharmacodynamics
Nevirapine functions as a non-nucleoside reverse transcriptase inhibitor (nNRTI) targeting HIV-1. It uniquely inhibits the reverse transcriptase enzyme, essential for the viral replication process, without affecting HIV-2 reverse transcriptase or eukaryotic DNA polymerases such as human DNA polymerases alpha, beta, or sigma. For optimal efficacy and to inhibit resistance, it is critical that nevirapine be used in combination with other HIV medications, such as Retrovir or Videx. It is important to note that viral resistance to nevirapine may develop if used alone, and its effectiveness is generally limited over time even with proper use.
Absorption
Nevirapine demonstrates excellent absorption, exceeding 90%, following oral administration in both healthy individuals and those with HIV-1 infection. The absolute bioavailability is substantial, recorded at 93 ± 9% for a 50 mg tablet and 91 ± 8% for an oral solution in healthy adults after a single dose. The peak plasma concentration of 2 ± 0.4 mcg/mL is typically achieved approximately four hours after a single 200 mg dose. The bioavailability of nevirapine tablets and suspension is comparable, validating their interchangeability for dosages up to 200 mg. Additionally, when taken with a high-fat meal, nevirapine's absorption remains consistent with that observed in the fasted state.
Metabolism
Nevirapine undergoes extensive hepatic metabolism, primarily via the cytochrome P450 3A4 enzyme system. Both in vivo studies in humans and in vitro research involving human liver microsomes have confirmed its transformation into multiple hydroxylated metabolites. This metabolic pathway underscores the importance of monitoring potential drug interactions and hepatic function during nevirapine therapy.
Mechanism of Action
Nevirapine acts by directly binding to reverse transcriptase, leading to an inhibition of its RNA-dependent and DNA-dependent DNA polymerase activities. This inhibition occurs through disruption of the enzyme's catalytic site. Notably, nevirapine's mechanism does not involve competition with either the template or nucleoside triphosphates.
