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March 4, 1997, Washington, DC - New information on VIRAMUNE® (nevirapine) was presented at the Fourth Conference on Retroviruses and Opportunistic Infections. The blood brain barrier (BBB) permeability of VIRAMUNE® was shown to be far superior to other antiretrovirals in both in vitro and in vivo animal models. "A critical issue in the treatment of HIV disease is the concern about reaching virus residing in difficult-to-reach sanctuaries, such as the brain," said Dr. Maureen Myers, Clinical Program Director of Virology at Boehringer Ingelheim Pharmaceuticals, Inc. "We now have new evidence that the pharmacologic properties of VIRAMUNE® make it an attractive candidate for studying antiretroviral effects on CNS viral load."
The new studies looked at how well HIV agents permeate the BBB, which may determine the success of attaining adequate drug levels in the human brain and central nervous system, long thought to be reservoirs of HIV. The in vitro model utilizes bovine brain microvessel endothelial cells to study and compare the ability of various drugs to cross the BBB. Four antiretrovirals, VIRAMUNE (nevirapine), zidovudine, indinavir, and delavirdine were studied in this model. At 10 to 100µM concentrations, VIRAMUNE® was five and ten times more permeable than zidovudine and indinavir, respectively. Delavirdine was the only drug that appeared not to cross the BBB. The in vitro results were supported by in vivo data derived from administration of the four antiretrovirals to rats and/or monkeys. These studies showed that the concentrations of VIRAMUNE® in brain tissue were equal to those in plasma in both rats and monkeys. However, neither indinavir nor delavirdine were found in rat brain at concentrations >1% of the simultaneous concentrations in plasma. Similarly, published data shows that zidovudine concentrations in rat brain reach only 10% of plasma concentrations. These results for VIRAMUNE® are consistent with the findings of a previous study in humans (n=6) in which VIRAMUNE® was found to be present in cerebrospinal fluid (CSF) in concentrations approximately equal to the fraction not bound to plasma protein. VIRAMUNE® is 60% protein bound (i.e. 40% free drug). The six children tested had VIRAMUNE® levels in the CSF which were 45% (±5%) of those in simultaneous plasma samples.
"Overall, these data support the contention that it may be possible to achieve inhibitory antiretroviral concentrations of VIRAMUNE® in the brain, where it may inhibit viral replication of HIV-1, potentially increasing its therapeutic value by reducing brain viral burden. However, studies in humans are necessary to confirm this activity," said Dr. Susan Hattox, Associate Director of Drug Metabolism & Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc. "This is exciting in that it may provide physicians with a drug that appears to reach one of the most protected areas of the body in an effort to reduce total viral burden."
VIRAMUNE® (nevirapine) is distributed by Roxane Laboratories, Inc., of Columbus, Ohio, a subsidiary of Boehringer Ingelheim Corporation. Roxane Laboratories is a leader in palliative care therapy and now manufactures a broad range of pharmaceuticals, including treatments for pain in AIDS and cancer, an antinauseant for cancer chemotherapy, and an appetite stimulant for AIDS. Boehringer Ingelheim Corporation is a member of the Boehringer Ingelheim worldwide group of companies, based in Ingelheim, Germany. A privately held company founded in 1885, Boehringer Ingelheim is a major pharmaceutical, chemical, animal health, and bakery products manufacturer with operations in more than 100 countries around the world. VIRAMUNE® is a product of original research done at Boehringer Ingelheim Pharmaceuticals, Inc., located in Ridgefield, CT, which is a sister company of Roxane Laboratories, Inc.
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