A Bioequivalence Study of Pyridoxine Hydrochloride and Doxylamine Succinate 20 mg/20 mg, Modified Release Tablets, Fixed Dose Combination in Healthy Female Adults

Objectives: This is a randomized, single-dose, two-period, two-sequence, and crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose formulations (FDC) of Pyridoxine 20 mg/Doxylamine 20 mg (P/D) modified release oral tablets in healthy female adults under fasting conditions. Materials and Methods: The plasma concentrations of P/D were measured using a validated liquid chromatography mass spectrometry method. Enrolled for the study were 44 female volunteers. Only 41 completed the study. The two formulations of P/D were considered bioequivalent if a 90% Confidence Interval (CI) for ln-transformed ratios of Cmax, AUC0-t and AUC0-inf fell within the acceptance range of 80.00 - 125.00%. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the Test formulation Pyridoxine 20 mg/Doxylamine 20 mg (T) and Reference formulation (R) Bonjesta® (Pyridoxine 20 mg /Doxylamine 20 mg), (90% CI for all PK parameters were within 80.00 - 125.00%). The 90% CI of the test/reference ratios of log-transformed PK parameter point estimates were to Cmax: 96.84% CIs (82.80 - 113.26), AUC0-t: 88.94% CIs (80.87 - 97.81) and AUC0-inf: 89.53% CIs (81.72 - 98.09) for Pyridoxine and Cmax: 89.45% CIs (84.54 - 94.64), AUC0-t: 91.04% CIs (86.63 - 95.68) and AUC0-inf: 90.81% CIs (86.30 - 95.56) for Doxylamine. Conclusion: Our results demonstrated BE between two FDC of P/D 20 mg/20 mg modified release formulations: Bonjesta® 20 mg/20 mg (Exeltis Health Care S.L) and Pyridoxine/Doxylamine 20 mg/20 mg (Laboratorios Leti, S.A.V) in healthy female adults under fasting conditions. P/D is a FDC considered the first line treatment of nausea and vomiting during pregnancy (NVP).