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- Title
PIII-35.
- Authors
Ma, Q.; Brazeau, D.; Zingman, B.; Reichman, R. C.; Fischl, M. A.; Gripshover, B.; Venuto, C.; Slish, J. C.; DiFrancesco, R.; Forrest, A.; Morse, G. D.
- Abstract
Background: The increasing interest in applying therapeutic drug monitoring (TDM) to antiretroviral therapy is related to the inter-individual variation in antiretroviral pharmacokinetics. This variation may be due to certain genetic variations such as the efflux pump P-glycoprotein MDR1 polymorphisms G2677T and C3435T.Method: To facilitate the application of TDM, a real-time PCR based genotyping method for the detection of MDR1 polymorphisms was developed in 62 HIV-positive patients. This method was used to determine the MDR1 genotypes in both substance abuser and non-abuser groups. The contribution of MDR1 polymorphisms to pharmacokinetic variability of antiretroviral therapy was further assessed.Results: Genotype assignments based on PCR growth curve, fluorescence melt-curve analysis, and gel electrophoresis of PCR products were in good agreement. Although no significant difference in MDR1 polymorphism distribution was noted between substance users and non-users (G=4.4, G2677T; G=0.6, C3435T), it appeared to be racially dependent with 75% and 92% African Americans having wild type C3435T and G2677T, versus 22% and 26% in Caucasians, respectively. A clear link between G2677T and C3435T was also noted. No relationship was observed in these initial patients between MDR1 genotypes and pharmacokinetic measures.Conclusion: This method is being incorporated into the TDM program implemented in the pharmacotherapy research center.Clinical Pharmacology & Therapeutics (2005) 79, P67–P67; doi: 10.1016/j.clpt.2005.12.243
- Subjects
SUBSTANCE abuse; HIV-positive persons; ANTIRETROVIRAL agents; GENETIC polymorphisms; AFRICAN Americans; PHARMACOKINETICS
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 79, Issue 2, pP67
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.12.243