Dependence of efavirenz- and rifampicin-isoniazid-based antituberculosis treatment drug-drug interaction on CYP2B6 and NAT2 genetic polymorphisms: ANRS 12154 study in Cambodia
| Autor: | Sao Sarady Ay, François-Xavier Blanc, Chantary Keo, Janin Nouhin, Lay Heng Chan, Borann Sar, Claire Rekacewicz, Nimul Roat Men, Chanthan Srey, Yoann Madec, Thim Sok, Julie Bertrand, Sokeo Chea, Marcelo Fernandez, Keo Kunthea Dy, Anne E. Goldfeld, Kimlay Chea, Manil Saman, Didier Laureillard, Pheakun Kry, Kerya Phon, Keolinelyanneth Meardey, Kunthea Kong, Olivier Marcy, Phearavin Pheng, Chanthy Leng, Céline Verstuyft, Monidarin Chou, Bertrand Guillard, Eric Nerrienet, Leakhena Say, Sopheak Ngin, Phalla Chea, Sirenda Vong, Laurence Borand, Sopheap Kun, Sarin Chan, Sophea Suom, Kuy Huong Nay, Yong Yoeun, Hok Kean Lim, Sophy Tun, Pichda Toeung, Kim Eng Sok, Anne-Marie Taburet, Sreymom Ken |
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| Rok vydání: | 2013 |
| Předmět: |
Cyclopropanes
Efavirenz Anti-HIV Agents Arylamine N-Acetyltransferase Antitubercular Agents HIV Infections Pharmacology Polymorphism Single Nucleotide chemistry.chemical_compound Plasma Pharmacokinetics immune system diseases parasitic diseases medicine Isoniazid Immunology and Allergy Humans Tuberculosis heterocyclic compounds Drug Interactions business.industry Stavudine virus diseases Lamivudine biochemical phenomena metabolism and nutrition Benzoxazines Cytochrome P-450 CYP2B6 Infectious Diseases chemistry Alkynes Spectrophotometry Ultraviolet Aryl Hydrocarbon Hydroxylases Rifampin business Cambodia Rifampicin Pharmacogenetics medicine.drug Chromatography Liquid |
| Zdroj: | The Journal of infectious diseases. 209(3) |
| ISSN: | 1537-6613 |
| Popis: | We investigated the population pharmacokinetics and pharmacogenetics of efavirenz in 307 patients coinfected with human immunodeficiency virus and tuberculosis and included in the Cambodian Early vs Late Initiation of Antiretrovirals trial (CAMELIA) in Cambodia. Efavirenz (600 mg/d) and stavudine plus lamivudine were administered in addition to standard antituberculosis treatment, including rifampicin and isoniazid. Blood samples were obtained a mean of 14 hours after efavirenz intake at weeks 2 and 6 after initiation of efavirenz and weeks 22 (efavirenz plus antituberculosis drugs) and 50 (efavirenz alone) after initiation of antituberculosis treatment. Ten patients participated in an extensive pharmacokinetic study after week 50. CYP2B6 G516T and C485-18T polymorphisms were the most significant covariates, with weight showing a significant minor effect. Change in efavirenz apparent clearance in patients taking both efavirenz and antituberculosis treatment was highly dependent on NAT2 polymorphism, as a possible surrogate of isoniazid exposure. Patients carrying the CYP2B6 516 TT genotype and slow-acetylation NAT2 phenotype had the lowest efavirenz apparent clearance. These data suggest that the inducing effect of rifampicin is counterbalanced by a concentration-dependant inhibitory effect of isoniazid on efavirenz clearance. Efavirenz is a nonnucleoside reverse-transcriptase inhibitor of human immunodeficiency virus (HIV) type 1 |
| Databáze: | OpenAIRE |
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