TITLE:
Pharmacokinetics and Bioequivalence of Dienogest in Healthy Bangladeshi Female Volunteers: An Open-Label, Single-Dose, Randomized, Two-Way Crossover Study
AUTHORS:
Nusrat Mahmud, Nafisa Ahamed, Uttom Kumar Bhowmik, Sabrina Akter Tushi, Nayan Ghosh, Nithon Chandra Sahana, Arifa Akram, Md. Alimur Reza
KEYWORDS:
Dienogest, Bioequivalence Study, Endometriosis, Novus CRSL
JOURNAL NAME:
Open Journal of Obstetrics and Gynecology,
Vol.14 No.5,
May
24,
2024
ABSTRACT: Background: Dienogest is a potential treatment for pelvic pain associated with endometriosis, a condition of significant concern in gynaecology. The current study was conducted as a crossover-randomized bioequivalence assessment of two oral Dienogest 2 mg formulations, aiming to provide valuable insights for healthcare professionals and researchers in this field. Objective: The primary aim of this research was to evaluate and compare the pharmacokinetic characteristics of Dienogest 2 mg tablets. Dinogest (Dienogest 2 mg) tablets, manufactured by Nuvista Pharma Limited in Bangladesh, and Visanne (Dienogest 2 mg) tablets, manufactured by Bayer Pharma in Germany, were the test and reference formulations, respectively. Materials and Method: The study was an open-label, balanced, randomized, two treatments, two sequences, two periods, two-way crossover, laboratory blind, single oral dose bioequivalence study conducted in healthy adult females under fasting conditions. The study was carried out on 13 healthy, non-pregnant female subjects, and all the subjects completed both study periods with a 15-day washout in between. Randomization was used to assign the test and reference formulations to the subjects. Following each oral administration, a series of blood samples were obtained at different time intervals from pre-dose to 72 hours post-dose and analyzed for Dienogest concentrations using a validated bio-analytical method. A standard non-compartmental model was used to analyze the pharmacokinetic parameters. The primary pharmacokinetic parameters were peak plasma drug concentration (Cmax), the area under the plasma concentration-time curve from time zero to time t (AUC0–t), and AUC from t = 0 to infinity (AUC0–∞). The other PK parameters included time to reach Cmax (Tmax), terminal elimination rate constant (Kel), and half-life (t1/2). Result: The ratios and 90% CI for the geometric mean test/reference were 95.53% (86.70% - 105.26%) for Cmax, 101.75% (95.42% - 108.49%) for AUC0−t, and 101.54% (95.59%% - 107.87%) for AUC0−∞. The formulations were bioequivalent since the 90% CIs for the geometric mean test/reference ratios were 80% to 125%, according to the predetermined range of US Food and Drug Administration (FDA) requirements. Conclusion: This single-dose investigation shows that the Dienogest test and reference formulations exhibited a rate and degree of absorption that met the regulatory requirements for bioequivalence.