Celecoxib-tramadol co-crystal: A Randomized 4-Way Crossover Comparative Bioavailability Study

PurposeCelecoxib-tramadol co-crystal (CTC) is a first-in-class of celecoxib and racemic tramadol. This Phase 1 bioavailability study compared single-dose pharmacokinetic (PK) parameters CTC with those the individual reference products from United States, immediate-release tramadol, taken alone simultaneously to determine their systemic exposure.MethodsThis was single-center, randomized, single-dose, open-label, 4-period, 4-sequence, crossover conducted in healthy subjects between October December 2016. Study treatments included 200-mg (equivalent 112-mg 88-mg tramadol; Treatment-1); 100-mg tramadol (Treatment-2); (Treatment-3); plus (Treatment-4). The PK interest were Cmax, AUC0–T, AUC0–∞, which also calculated normalized dose. Tmax only considered as supportive. statistical analysis based on parametric variance model parameters; two-sided 90% CI ratio geometric mean values for AUC0–∞ ln-transformed data, rank-transformed.FindingsThirty-six aged 18 55 years (21 male subjects, 15 female subjects; age, 35 years) participated study. Celecoxib presented lower reduced AUCs, faster Tmax. interference absorption when are administered together minimized CTC. For Treatment-1, -3, -4, 259, 318, 165 ng/mL (Cmax), respectively; 1930, 2348, 1929 ng • h/mL (AUC0–T); 1.5, 3.0, 2.5 hours (Tmax). Tramadol its active metabolite O-desmethyl Cmax AUCs well longer Tramadol/O-desmethyl -2, -4 214/55, 305/78, 312/78 Cmax; 2507/846, 2709/965, 2888/1010 AUC0–T; 3.0/4.0, 2.0/2.5, 1.9/2.5 Reported adverse events (none unexpected) occurred more frequently Treatment-2 Treatment-4.ImplicationsThe aim this compare profile US-marketed exposure validate dosing regimen subsequent pivotal factorial 3study. each component favorably modified by co-crystallization did not result higher celecoxib, concomitant administration. © 2021 Elsevier HS Journals, Inc.