Pharmacokinetics and bioequivalence study of Duonica®

Aim

To evaluate the pharmacokinetics, safety and bioequivalence of the test drug product Duonica® (INN: doxylamine + pyridoxine), enteric-coated tablets, 10 mg + 10 mg (Valenta Pharm JSC, Russia), and the reference drug product Diclectin®, delayed release tablets, 10 mg + 10 mg (Duchesnay Inc., Canada).

Material and methods

We conducted an open, randomized, two-period cross-over study of the comparative pharmacokinetics of the test drug product Duonica® and the reference drug product Diclectin® in healthy female volunteers after a single oral dose under fasting conditions. Twenty eight volunteers were randomly distributed into two groups of 14 each depending on the sequence of drug administration in periods 1 and 2. Plasma samples were taken at multiple points up to 72 h after dosing in each study period. The plasma concentrations of doxylamine and pyridoxal-5'-phosphate, the active metabolite of pyridoxine, were measured by high-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic and statistical analyses were performed and confidence intervals (CI) for the pharmacokinetic parameters Cmax and AUC(0-t) were calculated. The frequency and severity of adverse events (AEs) were recorded to evaluate the safety profile of the study drug products.

Results

For doxylamine, the 90% CI for the ratios of AUC(0-t) and Cmax values were 95.06–106.03% and 92.90–106.11%, respectively. For pyridoxal-5'-phosphate, the 90% CI for the ratios of AUC(0-72 h) and Cmax values were 94.74–111.81% and 98.53–109.80%, respectively. The 90% CIs were within the acceptance range 80.00–125.00% defined by the study protocol, indicating the bioequivalence of the test and reference medicinal products. No AEs were recorded during the study.

Conclusion

The pharmacokinetic parameters and safety profile of the test drug product Duonica® and the reference drug product Diclectin® were comparable.

Key words

Doxylamine, pyridoxine, pharmacokinetics, bioequivalence, nausea and vomiting during pregnancy.