Oral Boosting

The strategy of co-administration of anti-first pass effect compounds with other pharmaceuticals in order to enhance bioavailability is one that is well known in medicine. For example, the anti-fungal agent ketoconazole has been used to enhance the bioavailability of cyclosporine, an immunosuppressant used in transplant therapy. The commercial use of ketoconazole in this application has been hindered due to microbiological-safety issues that are inherent in administering any agent with antimicrobial activity to patients that do not possess a well-characterized and relevant infection. The BAS Boosters are not known to have any physiological activity other than CYP 3A inhibition.

In HIV therapy, the protease inhibitor ritonavir has been used as a booster to enhance the bioavailability of other, poorly bioavailable, protease inhibitors. In addition, ritonavir has been co-formulated with lopinavir, resulting in Abbott’s leading protease inhibitor, Kaletra™. In both instances ritonavir is given at a sub-therapeutic dose for its booster properties only. The approval of Kaletra™ in 2000 by the FDA validated the administration of anti-FPE compounds as an acceptable drug management practice. The prescription of ritonavir as a booster in this manner has been further legitimized by regulator approved label enhancement of the GSK protease inhibitor amprenavir, the Roche protease inhibitor saquinavir, the BMS proteaseinhibitor atazanavir, the Johnson & Johnson protease inhibitor darunavir, and the Boehringer-Ingelheim protease inhibitor tipranavir.

A further example of pharmacokinetic boosting is in the treatment of Parkinson’s disease through the co-administration of entacapone or tolcapone with L-Dopa and the co-formulation of entacapone with L-Dopa and cosbidopa. These boosters inhibit the breakdown of L-Dopa by the COMT enzyme before it reaches the brain. The FDA has approved both entacapone and tolcapone for co-administration with L-Dopa. A third example of boosting is the use of cilastatin, a renal dipeptidase inhibitor, to boost the antibiotic imipenem in Merck's Primaxin™.


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