Abstract
BackgroundMagnesium 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.MethodsTramadol 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.ResultsA 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+.ConclusionsThe 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.Graphic abstract
Highlights
Pain, especially chronic, decreases the quality of life and results in economic burdens for both individuals and the society in general [1]
Results of own studies and the literature data demonstrated that M g2+ increased opioid analgesia in experimental animal models of neuropathic [5,6,7], inflammatory [5], as well as acute [8,9,10] pain
Our work focuses on one of the group of opioid painkiller—tramadol
Summary
Especially chronic, decreases the quality of life and results in economic burdens for both individuals and the society in general [1]. 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. Mg2+ was administered orally at doses of 150 mg and 75 mg per tramadol dosing in a single- and multiple-dose study, respectively. Methods Tramadol was administered to healthy Caucasian subjects with and without Mg2+ as (1) single 100-mg and (2) multiple 50-mg oral doses. Results A total of 25 and 26 subjects completed the single- and multiple-dose study, respectively Both primary and secondary pharmacokinetic parameters were similar. Conclusions The absence of M g2+ interaction with tramadol pharmacokinetics and safety suggests that this combination may be used in the clinical practice for the pharmacotherapy of pain.
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