ABSTRACT
OBJECTIVE: 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. A 5-ml blood sample was collected before the daily intake of methadone. As a PD measure, the Subjective Opioid Withdrawal Scale (SOWS) 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 HPLC. Population PK/PD analysis was performed using population pharmacokinetics modeling software P-Pharm. RESULTS: Significant decreases (p< 0.05) were observed in the SOWS scores during 10 hours after methadone intake. The SOWS had returned to baseline by 24 hr after using methaodone (p= 0.98). A considerable interindividual variability in the CL/F (16 fold), EC50 (3 fold) and Emax (6 fold) for methadone was observed. CONCLUSION: 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 SOWS 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.
ABSTRACT
Extracts of five plants were investigated for their total flavonoids, phenol contents and their radical scavenging activity using DPPH assays: Polygonium hyrcanicum, Centaurea depressa, Sambucus ebulus, Mentha spicata and Phytolacca americana. Quercetin and butylated hydroxy toluene were used as standard reference with well-documented antioxidant activity. Total flavonoid content in these plants ranged from 31.6 to 109.5 mg g(-1) and the amount of free phenolic compounds was between 32 and 287.5 mg g(-1) extract powder. Free phenolic compounds content were in the order: P. hyrcanium > M. spicata > S. ebulus > C. depressa > P. americana. It was also observed that all methanolic extract samples of studied plants showed free radical scavenging activity. The highest antioxidant activity was found in P. hyrcanium with an IC 50 equal to 0.036 mg mL(-1) that is higher than BHT (IC 50 = 0.054). A correlation between radical scavenging capacities of extracts with total phenolic compounds content was observed. This result indicates that P. hyrcanium contains high levels of phenolic compounds that may contribute to higher free radical scavenging activity compared to the other extracts of the plants in this study.
