Pharmacokinetics of Tramadol and Celecoxib in Japanese and Caucasian Subjects Following Administration of Co-Crystal of Tramadol-Celecoxib (CTC): A Randomised, Open-Label Study
Abstract
BACKGROUND AND OBJECTIVES: Co-Crystal of Tramadol-Celecoxib (CTC) is a first-in-class active pharmaceutical ingredient (API-API) co-crystal of rac-tramadol.HCl and celecoxib in a 1:1 molecular ratio (100 mg CTC: 44 mg rac-tramadol.HCl and 56 mg celecoxib). Tramadol and celecoxib pharmacokinetics are modified after CTC administration versus administration of reference products. This randomised, open-label, crossover, phase 1 study assessed CTC pharmacokinetics, dose proportionality, safety and tolerability in Japanese and Caucasian subjects.
METHODS: CTC (100, 150 and 200 mg) was administered orally to healthy Japanese/Caucasian subjects. Tramadol, O-desmethyltramadol and celecoxib plasma concentrations were determined pre-dose and up to 48 h post-dose. Maximum observed plasma concentration (Cmax), and area under the plasma concentration-time curve from dosing to last measurable concentration (AUCt) and from dosing extrapolated to infinity (AUC∞) were evaluated. Dose proportionality was assessed in a dose-adjusted bioavailability analysis of variance and in a power model. Inter-cohort comparability of pharmacokinetic exposure was confirmed if the ratio (Japanese cohort/Caucasian cohort) of geometric least-squares means and corresponding 90% confidence intervals were 80-125%. Post hoc weight-adjusted comparability analyses were performed. Safety was assessed throughout.
RESULTS: Sixty subjects (21 males/9 females per cohort) were randomised; 57 completed the study. Cohorts…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial
- Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease
- Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience
- Celecoxib or naproxen treatment does not benefit depressive symptoms in persons aged 70 and over: findings from a randomized controlled trial
- Comparative Clinical Effectiveness of Nonsurgical Treatment Methods in Patients With Lumbar Spinal Stenosis: A Randomized Clinical Trial
- Efficacy and safety of adalimumab by intra-articular injection for moderate to severe knee osteoarthritis: An open-label randomized controlled trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.