Flexible dosing of Tincture of Opium in the management of opioid withdrawal: pharmacokinetics and pharmacodynamics

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dc.contributor.authorSomogyi, A.
dc.contributor.authorLarsen, M.
dc.contributor.authorAbadi, R.
dc.contributor.authorJittiwutikarn, J.
dc.contributor.authorAli, R.
dc.contributor.authorWhite, J.
dc.date.issued2008
dc.description.abstract<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.
dc.description.statementofresponsibilityAndrew A. Somogyi, Mie Larsen, Reza M. Abadi, Jaroon Jittiwutikarn, Robert Ali & Jason M. White
dc.identifier.citationBritish Journal of Clinical Pharmacology, 2008; 66(5):640-647
dc.identifier.doi10.1111/j.1365-2125.2008.03277.x
dc.identifier.issn0306-5251
dc.identifier.issn1365-2125
dc.identifier.orcidSomogyi, A. [0000-0003-4779-0380]
dc.identifier.orcidAli, R. [0000-0003-2905-8153]
dc.identifier.urihttp://hdl.handle.net/2440/52593
dc.language.isoen
dc.publisherBlackwell Publishing Ltd
dc.source.urihttps://doi.org/10.1111/j.1365-2125.2008.03277.x
dc.subjectopioid dependence
dc.subjectpharmacodynamics
dc.subjectpharmacokinetics
dc.subjectThailand
dc.subjecttincture of opium
dc.titleFlexible dosing of Tincture of Opium in the management of opioid withdrawal: pharmacokinetics and pharmacodynamics
dc.typeJournal article
pubs.publication-statusPublished

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