The Effect of Food on Tramadol and Celecoxib Bioavailability Following Oral Administration of Co-Crystal of Tramadol-Celecoxib (CTC): A Randomised, Open-Label, Single-Dose, Crossover Study in Healthy Volunteers
| Autor: | Eric Sicard, Neus Gascón, Mounia Lahjou, Marisol Escriche, Sebastián Videla, Mercedes Encabo, Carlos Plata-Salamán, Gregorio Encina, Kevin Smith |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Adolescent Cmax Biological Availability Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences Food-Drug Interactions Young Adult Tractament del dolor Analgèsics 0302 clinical medicine Pharmacokinetics Oral administration Pain treatment Medicine Humans Opiacis Pharmacology (medical) Original Research Article neoplasms Tramadol Analgesics Meal Cross-Over Studies Cyclooxygenase 2 Inhibitors business.industry General Medicine Fasting Middle Aged Crossover study Healthy Volunteers Bioavailability Opioids Analgesics Opioid Drug Combinations Celecoxib Area Under Curve Female business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Clinical Drug Investigation Dipòsit Digital de la UB Universidad de Barcelona |
| ISSN: | 1179-1918 |
| Popis: | Background and Objective Co-Crystal of Tramadol–Celecoxib (CTC), in development for the treatment of moderate to severe acute pain, is a first-in-class co-crystal containing a 1:1 molecular ratio of two active pharmaceutical ingredients; rac-tramadol·HCl and celecoxib. This randomised, open-label, crossover study compared the bioavailability of both components after CTC administration under fed and fasting conditions. Methods Healthy adults received single doses of 200 mg CTC under both fed and fasting conditions (separated by a 7-day washout). Each dose of CTC was administered orally as two 100 mg tablets, each containing 44 mg tramadol·HCl and 56 mg celecoxib. In the fed condition, a high-fat, high-calorie meal [in line with recommendations by the US Food and Drug Administration (FDA)] was served 30 min before CTC administration. Tramadol, O-desmethyltramadol and celecoxib plasma concentrations were measured pre- and post-dose up to 48 h. Pharmacokinetic parameters were calculated using non-compartmental analysis. Safety was also assessed. Results Thirty-six subjects (18 female/18 male) received one or both doses of CTC; 33 provided evaluable pharmacokinetic data under fed and fasting conditions. For tramadol and O-desmethyltramadol, fed-to-fasting ratios of geometric least-squares means and corresponding 90% confidence interval (CI) values for maximum plasma concentration (Cmax) and extrapolated area under the plasma concentration–time curve to infinity (AUC∞) were within the pre-defined range for comparative bioavailability (80–125%). For celecoxib, Cmax and AUC∞ fed-to-fasting ratios (90% CIs) were outside this range, at 130.91% (116.98–146.49) and 129.34% (121.78–137.38), respectively. The safety profile of CTC was similar in fed and fasting conditions. Conclusions As reported for standard-formulation celecoxib, food increased the bioavailability of celecoxib from single-dose CTC. Food had no effect on tramadol or O-desmethyltramadol bioavailability. Clinical trial registration number 152052 (registered with the Therapeutic Products Directorate of Health Canada) Electronic supplementary material The online version of this article (10.1007/s40261-018-0672-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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