The pharmacokinetics and pharmacodynamics of 17-d-norgestimate and ethinyl estradiol alone and in the presence of cilansetron 2 mg TID, in healthy females

Abstract

Background/Aims To assess the effects of cilansetron (CIL) 2 mg on the blood concentrations of ethinyl estradiol (EE), 17-d-Norgestimate (NG), progesterone (P), lutenizing hormone (LH), and follicle stimulating hormone (FSH) in healthy females receiving an oral contraceptive(OC). Methods Design A double-blind, balanced, randomized, two-period, placebo-controlled, cross-over study. Setting This study was conducted in a phase I clinic. Participants Twenty (20) females receiving OC daily for the first 21 days of two consecutive menstrual cycles. Intervention CIL 2 mg or placebo was administered orally three times daily from days 14 to 21 of each cycle. Blood samples for the measurement of PK and PD parameters were obtained. Statistical analysis of the PK and PD parameters was conducted using an ANOVA. Results (see Table) Conclusions Although EE levels were lower during co-administration of CIL (2 mg tid), no PK/PD interaction between CIL and EE and NG was observed in healthy females. Clinical Pharmacology & Therapeutics (2005) 77, P56–P56; doi: 10.1016/j.clpt.2004.12.103 Treatment1 Mean (SD) LS Mean2 (A/B) 90% CI EE AUC0-24(hr*ng/ml) A 1.21 (0.55) 1.07 90.15 (85.76–94.76) B 1.32 (0.57) 1.18 - - Cmax (ng/ml) A 0.14 (0.06) 0.13 91.87 (84.76–99.58) B 0.16 (0.06) 0.14 - - NG AUC(hr*ng/ml) A 18.90 (5.75) 17.34 97.29 (91.48–103.47) B 19.47 (6.08) 17.82 - - Cmax (ng/ml) A 2.33 (0.89) 2.09 101.87 (90.09–115.20) B 2.29 (0.79) 2.06 - - 1 A=OC+CIL, B=OC+Placebo Least Squares Mean. No difference was observed in blood levels of P, LH and FSH in the presence of CIL