Somogyi, A.Larsen, M.Abadi, R.Jittiwutikarn, J.Ali, R.White, J.2009-11-102009-11-102008British Journal of Clinical Pharmacology, 2008; 66(5):640-6470306-52511365-2125http://hdl.handle.net/2440/52593<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>The management of opioid withdrawal can be achieved, with minimal adverse effects, by using flexible dosing of TOP.enopioid dependencepharmacodynamicspharmacokineticsThailandtincture of opiumJournal article002008334010.1111/j.1365-2125.2008.03277.x0002604987000072-s2.0-5514910569141499Somogyi, A. [0000-0003-4779-0380]Ali, R. [0000-0003-2905-8153]