Associations between CYP2B6 polymorphisms and pharmacokinetics after a single dose of nevirapine or efavirenz in African americans.
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| Grant Information: | P30 AI054999-06 United States AI NIAID NIH HHS; P01 GM031304 United States GM NIGMS NIH HHS; UL1 RR024975-01 United States RR NCRR NIH HHS; AI071205 United States AI NIAID NIH HHS; P30 AI054999 United States AI NIAID NIH HHS; TL1 RR024978 United States RR NCRR NIH HHS; KL2 RR024977 United States RR NCRR NIH HHS; R01 AI058696 United States AI NIAID NIH HHS; AI54999 United States AI NIAID NIH HHS; RR024975 United States RR NCRR NIH HHS; GM31304 United States GM NIGMS NIH HHS; R01 MH071205 United States MH NIMH NIH HHS; R01 AI058696-03 United States AI NIAID NIH HHS; P01 GM031304-24 United States GM NIGMS NIH HHS; AI058696 United States AI NIAID NIH HHS; MH071205 United States MH NIMH NIH HHS; R01 MH071205-05 United States MH NIMH NIH HHS; UL1 RR024975 United States RR NCRR NIH HHS |
| Substance Nomenclature: | 0 (Alkynes) 0 (Anti-HIV Agents) 0 (Benzoxazines) 0 (Cyclopropanes) 99DK7FVK1H (Nevirapine) EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases) EC 1.14.14.1 (CYP2B6 protein, human) EC 1.14.14.1 (Cytochrome P-450 CYP2B6) EC 1.5.- (Oxidoreductases, N-Demethylating) JE6H2O27P8 (efavirenz) |
| Entry Date(s): | Date Created: 20090226 Date Completed: 20090529 Latest Revision: 20240712 |
| Update Code: | 20240712 |
| PubMed Central ID: | PMC2784690 |
| DOI: | 10.1086/597125 |
| PMID: | 19239339 |
| Autor: | Haas DW; USA. david.w.haas@vanderbilt.edu, Gebretsadik T, Mayo G, Menon UN, Acosta EP, Shintani A, Floyd M, Stein CM, Wilkinson GR |
| Jazyk: | angličtina |
| Zdroj: | The Journal of infectious diseases [J Infect Dis] 2009 Mar 15; Vol. 199 (6), pp. 872-80. |
| DOI: | 10.1086/597125 |
| Abstrakt: | Background: Polymorphisms in CYP2B6 affect the steady-state plasma concentrations of nevirapine and efavirenz. In many resource-limited countries, a single dose of nevirapine has been widely prescribed to pregnant women at delivery, to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). We characterized associations between genetic polymorphisms and the pharmacokinetics of single doses of nevirapine and efavirenz. Methods: Plasma drug concentrations were determined over the 13-day period after administration of a 200-mg oral dose of nevirapine to nonpregnant, HIV-negative African Americans. A 600-mg oral dose of efavirenz was subsequently administered, and pharmacokinetic sampling was repeated. Pharmacokinetic parameters were estimated using a noncompartmental approach. Primary analyses involved 2 CYP2B6 polymorphisms (516G --> T and 983T --> C) known to predict increased steady-state plasma nevirapine and efavirenz exposure. Exploratory analyses involved another 51 polymorphisms in CYP2B6, ABCB1, CYP3A4, and CYP3A5. Results: On the basis of the composite CYP2B6 516/983 genotype, the 34 participants comprised 10 extensive, 17 intermediate, and 7 slow metabolizer genotypes. The composite CYP2B6 516/983 genotype was significantly associated with plasma drug exposure and clearance for efavirenz but not nevirapine. Exploratory analyses suggested possible associations between additional CYP2B6 polymorphisms and the pharmacokinetics of nevirapine and efavirenz. Conclusions: Selective pressure for drug-resistant HIV-1 after administration of single-dose nevirapine may not differ substantially according to CYP2B6 516/983 genotype. Additional polymorphisms, genes, and populations warrant further study. |
| Databáze: | MEDLINE |
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