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.
Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avda. de la Universidad s/n, Elche, Alicante, Spain. jesteban@umh.es
Javier
J
Esteban
María de la Cruz
Mde L
Pellín
Carmen
C
Gimeno
José
J
Barril
Jesús
J
Giménez
Eva
E
Mora
Adolfo G
AG
Garcia-Pérez
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