Article

Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin coadministration

Government of Tamil Nadu, Mathurai, Tamil Nadu, India
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 06/2006; 42(1):36-41. DOI: 10.1097/01.qai.0000214808.75594.73
Source: PubMed

ABSTRACT 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 HIV-infected patients on regular antiretroviral treatment with nevirapine-containing regimens (200 mg twice daily). A baseline 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 <.01). The Cmin of nevirapine fell below the therapeutic range of 3 microg/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 microg/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.

Full-text

Available from: Sikhamani Rajasekaran, Dec 14, 2013
0 Bookmarks
 · 
96 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To systematize information about drug interactions in HIV/AIDS, and to test a proposal to identify and evaluate drug interactions considered clinically relevant highlight those associated to pharmacokinetic mechanism. Method We performed a MEDLINE search of the literature published in English and Spanish from January 1995 to June 2007 on antiretroviral drug interactions in humans. Search terms were drug interactions and antiretroviral agents (or drugs) in title/abstract field. So, we searched for clinically relevant drug interactions of specific drugs commonly administered to patients with HIV, and we reviewed references cited in relevant articles. Finally, we followed a proposal to evaluate and use the clinical relevance complemented with a classification based on severity and probability of its occurrence. Results A total of 378 articles were achieved, among then we acquire the full text of 296. We presented the type and mechanism of drug interactions in HIV-infected patients. We evaluate and use the clinical relevance of drug interactions. Among pharmacokinetic interactions considered clinically relevant, approximately to 80% was related to changes in systemic clearance [due to induction or inhibition of systemic metabolic activity of cytochrome P450 3A4 (CYP3A4)]; and 15% with changes in bioavailability [(due to changes in gastrointestinal pH, presystemic metabolism or activity of the glicoprotein –P (Gp-P)]. Conclusions Among patients with HIV/AIDS, most of the pharmcokinetic interactions of clinical relevance are attributed to inhibition or induction of hepatic systemic metabolic activity, mainly of CYP3A4.
    Farmacia Hospitalaria 01/2007; 31(5):283–302. DOI:10.1016/S1130-6343(07)75392-8
  • [Show abstract] [Hide abstract]
    ABSTRACT: The heterogeneous carbonyl allylation of aldehydes and ketones with allylic chlorides was achieved in DMF using SnCl2 as reducing agent at 25–40°C in the presence of a 3-(2-aminoethylamino)propyl-functionalized MCM-41-immobilized palladium(II) complex [MCM-41-2N-Pd(II)], yielding a variety of homoallylic alcohols in good to high yields. This heterogeneous palladium catalyst exhibited higher activity than (N-propylethylenediamine)PdCl2 and can be recovered and recycled by a simple filtration of the reaction solution and used for at least 5 consecutive trials without any decreases in activity.
    ChemInform 09/2011; 696(10):2030-2034. DOI:10.1016/j.jorganchem.2010.10.055
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ESC 1753 1763 2401 0.60 (0.5-0.8) 0.60 (0.4-0.9) FDN 3148 2920 2702 1.11 (1.0-1.2) 1.08 (0.9-1.3) *P value 0.01 0.08 0.73 AUC 0-12 ng.h/mL ESC 25223 23668 32606 0.72 (0.6-0.9) 0.57 (0.5 -0.7) FDN 43195 44918 41997 1.03 (0.9-1.1) 1.07 ( 1.0-1.1) *P value