AIMS: The aim was to evaluate the clinical effectiveness, pharmacodynamics and pharmacokinetics of a range of Tincture of Opium (TOP) doses in the management of opioid withdrawal. METHODS:Forty-five opium-dependent Thai subjects were allocated to three dosing groups (6.66, 13.3 and 20 mg morphine equivalents, twice daily) depending on their self-reported prior opium use. On day 5 of dosing subjects underwent an interdosing interval study where blood, withdrawal scores, heart rate and blood pressure (BP) were collected at 0, 1, 3 and 8 h. Plasma morphine concentrations were quantified by high-performance liquid chromatography, and plasma morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations by LCMS. RESULTS:Thirty-two subjects completed the study. Withdrawal scores were low for all subjects (range 9-23% of maximum response). There were dose-dependent changes in both systolic and diastolic BP (P = 0.021 and P = 0.01, respectively), but these were not considered clinically significant. There were no effects of dose on respiratory rate. Plasma morphine concentrations changed significantly across the interdosing interval (P = 0.0001), rising to a maximum at 1 h after dosing. Plasma morphine concentrations also differed according to dose (P < 0.05). The mean ratios of the morphine glucuronides were found to be: M3G/M6G = 7.7, M3G/morphine = 35.6 and M6G/morphine = 4.9, values comparable to those previously reported. CONCLUSION: The management of opioid withdrawal can be achieved, with minimal adverse effects, by using flexible dosing of TOP.
RCT Entities:
AIMS: The aim was to evaluate the clinical effectiveness, pharmacodynamics and pharmacokinetics of a range of Tincture of Opium (TOP) doses in the management of opioid withdrawal. METHODS: Forty-five opium-dependent Thai subjects were allocated to three dosing groups (6.66, 13.3 and 20 mg morphine equivalents, twice daily) depending on their self-reported prior opium use. On day 5 of dosing subjects underwent an interdosing interval study where blood, withdrawal scores, heart rate and blood pressure (BP) were collected at 0, 1, 3 and 8 h. Plasma morphine concentrations were quantified by high-performance liquid chromatography, and plasma morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations by LCMS. RESULTS: Thirty-two subjects completed the study. Withdrawal scores were low for all subjects (range 9-23% of maximum response). There were dose-dependent changes in both systolic and diastolic BP (P = 0.021 and P = 0.01, respectively), but these were not considered clinically significant. There were no effects of dose on respiratory rate. Plasma morphine concentrations changed significantly across the interdosing interval (P = 0.0001), rising to a maximum at 1 h after dosing. Plasma morphine concentrations also differed according to dose (P < 0.05). The mean ratios of the morphineglucuronides were found to be: M3G/M6G = 7.7, M3G/morphine = 35.6 and M6G/morphine = 4.9, values comparable to those previously reported. CONCLUSION: The management of opioid withdrawal can be achieved, with minimal adverse effects, by using flexible dosing of TOP.
Authors: Jaroon Jittiwutikarn; Robert Ali; Jason M White; Felix Bochner; Andrew A Somogyi; David J R Foster Journal: Br J Clin Pharmacol Date: 2004-11 Impact factor: 4.335
Authors: Eloise A Gelston; Janet K Coller; Olga V Lopatko; Heather M James; Helmut Schmidt; Jason M White; Andrew A Somogyi Journal: Br J Clin Pharmacol Date: 2012-05 Impact factor: 4.335