title: [Cytochrome P450 and NAT2 polymorphisms and drug metabolism in DOTS].
abstract: It has been described an increase of the frequency of Directly Observed Therapy Short-course (DOTS) failure in countries with high rates of mycobacterial drug resistance. This increase could be due to the standardized doses of DOTS results in low or insufficient dosage of drugs in plasma. Several members of cytochrome P450 enzymes superfamily could explain the variations on acetylation velocity and in drug disposition. A population with slow acetylation has a higher risk of toxicity, as that potent inhibition of cytochrome P450 (CYP450) isoforms by isoniazid (CYP2C19 y CYP3A) are dependent of INH plasmatic concentration. This inhibitory effect has been described also for CYP12, CYP2C9 and CYP2E1. INH is metabolized by N-acetyltransferase 2 (NAT2). The wide variability interethnic and intraethnic in acetylation velocity is associated with the polymorphisms of NAT2. Patients with rapid acetylation have plasmatic concentration of INH low or insufficient which induces treatment failure. The study of genotypes of P450 and NAT2 allow us to predict therapeutic and individualized dosages.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, México, DF.
authors.forename: Manuel de J
authors.initials: Mde J
authors.lastname: Castillejos-López
authors.forename: Ma Cecilia
authors.initials: MC
authors.lastname: García-Sancho
authors.forename: Francisco
authors.initials: F
authors.lastname: Quiñones-Falconi
authors.forename: José R
authors.initials: JR
authors.lastname: Pérez-Padilla
mesh_terms: D000107:Acetylation; D000995:Antitubercular Agents / Q000378:metabolism*; D001191:Arylamine N-Acetyltransferase / Q000187:drug effects* / Q000235:genetics*; D002985:Clinical Protocols; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007538:Isoniazid / Q000378:metabolism*; D011110:Polymorphism, Genetic; D044469:Racial Groups; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D003577:Cytochrome P-450 Enzyme System; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid