Piotr J Rudzki1, Katarzyna Jarus-Dziedzic2, Monika Filist1, Edyta Gilant1, Katarzyna Buś-Kwaśnik1, Andrzej Leś1, Małgorzata Sasinowska-Motyl3, Łukasz Nagraba4, Magdalena Bujalska-Zadrożny5. 1. Łukasiewicz Research Network - Pharmaceutical Research Institute, ul. Rydygiera 8, 02-091, Warsaw, Poland. 2. BioVirtus Research Site Sp, ul. Borowa 14/18, 05-400, Otwock, Poland. 3. Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, ul. Banacha 1b, 01-793, Warsaw, Poland. 4. Orthopedic and Rehabilitation Department, Medical University of Warsaw, ul. Kondratowicza 8, 03-242, Warsaw, Poland. 5. Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, ul. Banacha 1b, 01-793, Warsaw, Poland. magdalena.bujalska@wum.edu.pl.
Abstract
BACKGROUND:Magnesium ions (Mg2+) increase and prolong opioid analgesia in chronic and acute pain. The nature of this synergistic analgesic interaction has not yet been explained. Our aim was to investigate whether Mg2+ alter tramadol pharmacokinetics. Our secondary goal was to assess the safety of the combination. METHODS:Tramadol was administered to healthy Caucasian subjects with and without Mg2+ as (1) single 100-mg and (2) multiple 50-mg oral doses. Mg2+ was administered orally at doses of 150 mg and 75 mg per tramadol dosing in a single- and multiple-dose study, respectively. Both studies were randomized, open label, laboratory-blinded, two-period, two-treatment, crossover trials. The plasma concentrations of tramadol and its active metabolite, O-desmethyltramadol, were measured. RESULTS:A total of 25 and 26 subjects completed the single- and multiple-dose study, respectively. Both primary and secondary pharmacokinetic parameters were similar. The 90% confidence intervals for Cmax and AUC0-tgeometric mean ratios for tramadol were 91.95-102.40% and 93.22-102.76%. The 90% confidence intervals for Cmax,ss and AUC0-τ geometric mean ratios for tramadol were 93.85-103.31% and 99.04-105.27%. The 90% confidence intervals for primary pharmacokinetic parameters were within the acceptance range. ANOVA did not show any statistically significant contribution of the formulation factor (p > 0.05) in either study. Adverse events and clinical safety were similar in the presence and absence of Mg2+. CONCLUSIONS: The absence of Mg2+ interaction with tramadol pharmacokinetics and safety suggests that this combination may be used in the clinical practice for the pharmacotherapy of pain.
RCT Entities:
BACKGROUND:Magnesium ions (Mg2+) increase and prolong opioid analgesia in chronic and acute pain. The nature of this synergistic analgesic interaction has not yet been explained. Our aim was to investigate whether Mg2+ alter tramadol pharmacokinetics. Our secondary goal was to assess the safety of the combination. METHODS:Tramadol was administered to healthy Caucasian subjects with and without Mg2+ as (1) single 100-mg and (2) multiple 50-mg oral doses. Mg2+ was administered orally at doses of 150 mg and 75 mg per tramadol dosing in a single- and multiple-dose study, respectively. Both studies were randomized, open label, laboratory-blinded, two-period, two-treatment, crossover trials. The plasma concentrations of tramadol and its active metabolite, O-desmethyltramadol, were measured. RESULTS: A total of 25 and 26 subjects completed the single- and multiple-dose study, respectively. Both primary and secondary pharmacokinetic parameters were similar. The 90% confidence intervals for Cmax and AUC0-t geometric mean ratios for tramadol were 91.95-102.40% and 93.22-102.76%. The 90% confidence intervals for Cmax,ss and AUC0-τ geometric mean ratios for tramadol were 93.85-103.31% and 99.04-105.27%. The 90% confidence intervals for primary pharmacokinetic parameters were within the acceptance range. ANOVA did not show any statistically significant contribution of the formulation factor (p > 0.05) in either study. Adverse events and clinical safety were similar in the presence and absence of Mg2+. CONCLUSIONS: The absence of Mg2+ interaction with tramadol pharmacokinetics and safety suggests that this combination may be used in the clinical practice for the pharmacotherapy of pain.
Entities:
Keywords:
Drug interaction; O-Desmethyltramadol; Opioid analgesia; Pain treatment; Pharmacokinetics; Tramadol
Authors: H J Jabbour; N M Naccache; R J Jawish; H A Abou Zeid; K B Jabbour; L G Rabbaa-Khabbaz; I B Ghanem; P H Yazbeck Journal: Acta Anaesthesiol Scand Date: 2014-03-17 Impact factor: 2.105
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