Plasma levels and pharmacokinetics of norethindrone and ethinylestradiol administered in solution and as tablets to women.
Twenty-four normal adult female volunteers were dosed orally with a solution and tablet formulation containing the contraceptive combination of norethindrone (NET, 1.0 mg) and ethinylestradiol (EE2, 0.12 mg) in a crossover bioequivalence study. Blood was sampled sequentially following single oral doses and the plasma separated for analysis of NET and EE2 by specific radioimmunoassays. Comparisons of both drugs following a dose in solution and tablets were made with respect to the following parameters: (a) plasma concentrations at each sample time; (b) maximum plasma concentration (Cpmax); (c) time to maximum plasma concentration (Tmax); (d) total area under the plasma concentration vs. time curve (AUC), and (e) plasma half-life (t1/2). It was found that the tablet and solution doses were bioequivalent with respect to EE2 absorption. However, absorption of NET from solution and tablet doses exhibited significant differences with respect to plasma levels at certain time points as well as AUC (which were higher following the tablet dose), but Cpmax, Tmax and t1/2 were not significantly different. Pharmacokinetic analysis of both drugs following the tablet dose was carried out using a two-compartment open model. The absorption rate constant (ka) and peripheral to central compartment transfer rate constant (k21) were similar for NET and EE2, but statistically significant differences were observed with respect to the distribution rate constant (alpha), the central to peripheral transfer rate constant (k12), the overall elimination rate constant (ke1), and volume of distribution (V1/F). The elimination rate constant (beta) for both drugs showed a difference of borderline statistical significance.
D000293:Adolescent; D000327:Adsorption; D000328:Adult; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000097:blood*; D011863:Radioimmunoassay; D012996:Solutions; D013607:Tablets
D012996:Solutions; D013607:Tablets; D004997:Ethinyl Estradiol; D009640:Norethindrone