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Nevirapine has excellent blood brain barrier permeability and absorption properties compared to other HIV antiretrovirals.
Yazdanian M; Glynn SL; Boehringer Ingelheim Pharm. Inc., Ridgefield, CT
December 30, 1998
Int Conf AIDS. 1998;12:1016 (abstract no. 60086). Unique Identifier :

BACKGROUND: To combat infection and inhibit viral replication of HIV both systemically and in the central nervous system, antiretroviral agents must have good oral absorption and be able to cross the blood brain barrier (BBB). METHODS: In vitro models for determination of BBB permeability using brain microvessel endothelial cells and oral absorption using Caco-2 cells were employed. In each model, cells were grown as monolayers on porous filters to study and compare the transport of nevirapine, a potent and selective non-nucleoside reverse transcriptase inhibitor, with other HIV antiretroviral agents currently in use for the treatment of HIV infection. These included nucleoside reverse transcriptase inhibitors (didanosine, stavudine, zalcitabine, zidovudine), a non-nucleoside reverse transcriptase (delaviridine), and protease inhibitors (indinavir, saquinavir, VX-478). RESULTS: Nevirapine was the most permeable antiretroviral agent in both models. The order in vitro BBB permeability was: nevirapine >> VX-478 > didanosine, stavudine, zalcitabine, zidovudine > indinavir > saquinavir whereas the order of Caco-2 cell permeability was: nevirapine > VX-478 > zidovudine > saquinavir > stavudine > didanosine, zalcitabine, indinavir. There were no significant effects on either BBB or Caco-2 cell permeability of nevirapine in combination with other antiRetroviral agents. Saquinavir and indinavir were shown to have an affinity for the P-glycoprotein efflux pumps which may have contributed to lowering their cellular permeability values. CONCLUSIONS: The apparent ability of nevirapine to be highly absorbed from the gastrointestinal tract as well as readily cross the BBB and enter the brain, where it can inhibit replication of HIV, may significantly increase its therapeutic value for the CNS treatment of HIV infection.

MEETING ABSTRACTS Anti-HIV Agents/*PHARMACOKINETICS *Blood-Brain Barrier/DRUG EFFECTS Brain/BLOOD SUPPLY Caco-2 Cells Cell Membrane Permeability/DRUG EFFECTS Comparative Study Endothelium, Vascular/METABOLISM Human HIV/DRUG EFFECTS In Vitro *Intestinal Absorption/DRUG EFFECTS Nevirapine/*PHARMACOKINETICS Virus Replication/DRUG EFFECTS