population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of methadone in a sample of iranian (mazandarani) opiate users undergoing methadone maintenance treatment

ôbjective: to investigate the pharmacokinetics (pk) and pk- pharmacodynamic (pd) relationship of methadone in a cohort of outpatients undergoing methadone maintenance treatment (mmt). methods: sixty male patients undergoing mmt with a mean ±sd methadone daily dosage of 58 ± 34 mg were enrolled in this study. â 5-ml blood sample was collected before the daily intake of methadone. âs a pd measure, the subjective ôpioid withdrawal scale (sôws) form was completed immediately after obtaining the blood sample. blood samples were taken and the forms were completed 4-5 times more (up to 24 hr) after the daily intake of methadone. plasma methadone was analyzed using hplç. population pk/pd analysis was performed using population pharmacokinetics modeling software p-pharm. results: significant decreases (p< 0.05) were observed in the sôws scores during 10 hours after methadone intake. the sôws had returned to baseline by 24 hr after using methaodone (p= 0.98). â considerable interindividual variability in the çl/f (16 fold), ëç50 (3 fold) and ëmax (6 fold) for methadone was observed. çonclusion: withdrawal symptoms were significantly improved in mmt patients after taking methadone and the pd measure was substantially affected by fluctuations in plasma methadone concentration. however, the sôws had returned to baseline by 24 hr after using mathadone. thus, a once daily dosing of methadone may not be suitable for those mmt patients who experience a significant withdrawal disturbance in the latter part of the interdose interval. this may increase the perceived severity of withdrawal and induce a craving for additional opioids.