Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies
| Autor: | Łukasz Nagraba, Katarzyna Buś-Kwaśnik, Monika Filist, Piotr J. Rudzki, Andrzej Leś, Katarzyna Jarus-Dziedzic, Edyta Gilant, Małgorzata Sasinowska-Motyl, Magdalena Bujalska-Zadrożny |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Drug interaction Analgesic Cmax Administration Oral 030226 pharmacology & pharmacy Drug Administration Schedule Article 03 medical and health sciences Young Adult 0302 clinical medicine Opioid analgesia Pharmacokinetics medicine Humans Pain treatment Drug Interactions Magnesium Magnesium ion Active metabolite Tramadol Pharmacology O-Desmethyltramadol Cross-Over Studies Dose-Response Relationship Drug business.industry General Medicine Analgesics Opioid Opioid Anesthesia Area Under Curve Female business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Pharmacological Reports |
| ISSN: | 2299-5684 |
| Popis: | 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. Graphic abstract |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink