Increase of R-/S-methadone enantiomer concentration ratio in serum of patients treated with either nevirapine or efavirenz.
An increased methadone enantiomer ratio (R/S) was associated to both nevirapine (179%, n=5) and efavirenz (36%, n=9) treatments when compared with that of controls (n=52). Additionally, in four follow-up patients, both R- and S-methadone normalized concentrations decreased (19%-93%) while R/S increased (22%-314%) following nevirapine/efavirenz treatment. R/S decreased (42%) after non-compliance with efavirenz treatment. Therefore, the methadone-maintenance-treatment outcome should be evaluated when patients are treated with drugs which are supposed to induce CYP3A4 and CYP2B6 isoforms.
Esteban
Javier
J
Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avda. de la Universidad s/n, Elche, Alicante, Spain. jesteban@umh.es
Pellín
María de la Cruz
Mde L
Gimeno
Carmen
C
Barril
José
J
Giménez
Jesús
J
Mora
Eva
E
Garcia-Pérez
Adolfo G
AG
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects / Q000378:metabolism; D048588:Benzoxazines / Q000494:pharmacology*; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008691:Methadone / Q000493:pharmacokinetics*; D009294:Narcotics / Q000493:pharmacokinetics*; D019829:Nevirapine / Q000494:pharmacology*; D010089:Oxidoreductases, N-Demethylating / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009294:Narcotics; D019829:Nevirapine; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz; D008691:Methadone