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Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin coadministration

Ramachandran, Geetha and Hemanth Kumar, A K and Rajasekaran, S and Padmapriyadarshini, C and Narendran, G and Sukumar, B and Sathishnarayan, S and Raja, K and Kumaraswami, V and Swaminathan, Soumya (2006) Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin coadministration. Journal of Acquired Immune Deficiency Syndromes, 42 (1). pp. 36-41. ISSN Print: 1525-4135; Online 1077-9450

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We studied the effect of rifampicin on steady-state pharmacokinetics of nevirapine and the impact of increasing the dose of nevirapine on its peak (Cmax) and trough (Cmin) levels in 13 HIVinfected patients on regular antiretroviral treatment with nevirapinecontaining regimens (200 mg twice daily).Abaseline pharmacokinetic study was conducted and repeated after 1 week of daily rifampicin (450/600 mg). The study was repeated in 7 of 8 patients who had subtherapeutic Cmin nevirapine levels after increasing nevirapine dose to 300 mg twice daily. Liver function was monitored. Rifampicin caused significant reductions in Cmax (42%), Cmin (53%), and exposure (46%) of nevirapine (P G .01). The Cmin of nevirapine fell below the therapeutic range of 3 Kg/mL in 8 of 13 patients. An increase of nevirapine to 300 mg twice daily raised Cmin to therapeutic range in all 7 patients without exceeding the toxic level of 12 Kg/mL. There were no clinical or laboratory adverse events. Our findings suggest that decreased bioavailability of nevirapine because of rifampicin coadministration could be overcome by increasing the dose of nevirapine from 200 to 300 mg twice daily without short-term adverse events. Further studies to evaluate the long-term safety of higher dose of nevirapine are required.

Item Type: Article
Uncontrolled Keywords: HIV-TB, pharmacokinetic drug interactions, nevirapine, rifampicin
Subjects: Tuberculosis > Laboratory Research > Biochemical,Clinical and Pharmacological
Divisions: Basic Science Research > Biochemistry and Pharmacology
Depositing User: Dr. Rathinasabapati R
Date Deposited: 03 Dec 2013 10:48
Last Modified: 09 Mar 2016 06:20

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