Nevirapine (NVP) is a benzodiazepine non-nucleoside reverse transcriptase inhibitor. In combination with other antiretroviral drugs, nevirapine reduces HIV viral loads and increases CD4 counts, thereby retarding or preventing the damage to the immune system and reducing the risk of developing AIDS.

HIV-1:270 μM(ki)

In various animal models, the metabolism of Nevirapine (NVP) proceeds as follows: One of the primary metabolites identified in the feces of all tested animals, except male rats, is 3-HydroxylNVP (3-OHNVP). For all male subjects as well as female mice, dogs, and monkeys, one of the principal metabolites is 4-Carboxylic AcidNVP (4-CANVP). Additionally, the predominant metabolites in rat bile are found to be 4-CANVP and a glucuronide conjugate of 12-HydroxylNVP (12-OHNVPglucuronide).

Nevirapine (NVP) acts primarily as a CYP3A4 inhibitor, with its inhibitory concentration significantly higher than the concentration related to its therapeutic use (Ki: 270 μM). As a non-nucleoside reverse transcriptase inhibitor, Nevirapine effectively inhibits reverse transcriptase from retroviruses, and it also inhibits endogenous reverse transcription in both mouse and human cell lines. Additionally, Nevirapine has been shown to alleviate the differentiation block in cell lines and primary cells from acute myeloid leukemia (AML) patients, as indicated by morphological, functional, and immunophenotypic analyses. It alters the cleavage specificity of RNAse H, resulting in Nevirapine-induced RNase H activity that exceeds the expected changes in cleavage specificity. Nevirapine is a highly specific inhibitor of HIV-1 reverse transcriptase (RT), with an IC50 of 84 nM in enzyme assays and an IC50 of 40 nM against HIV-1 replication in cell cultures.

FRO cells are seeded into 96-well culture plates at 10,000 cells/well. Cells are treated with different doses of nevirapine (0, 100, 200, 350 and 500 μM) for 48 h. MTT dye (5 mg/mL) is added to each well for additional 4 h, and the reaction is then stopped by the addition of DMSO. Optical density is measured at 490 nm on a multi-well plate reader[2].