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The pharmacokinetics and pharmacodynamics of 17‐d‐norgestimate and ethinyl estradiol alone and in the presence of cilansetron 2 mg TID, in healthy females
Author(s) -
ZumBrunnen T. L.,
Boon P.,
Chang J.,
deVries M.,
Brennan J. J.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.103
Subject(s) - pharmacokinetics , cmax , medicine , placebo , pharmacodynamics , ethinylestradiol , follicle stimulating hormone , analysis of variance , endocrinology , hormone , luteinizing hormone , pharmacology , population , research methodology , alternative medicine , environmental health , pathology
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.2004.12.103Treatment 1 Mean (SD) LS Mean 2 (A/B) 90% CIEEAUC0‐24(hr*ng/ml) A 1.21 (0.55) 1.07 90.15 (85.76–94.76) B 1.32 (0.57) 1.18 ‐ ‐ C max (ng/ml) A 0.14 (0.06) 0.13 91.87 (84.76–99.58)B 0.16 (0.06) 0.14 ‐ ‐NGAUC(hr*ng/ml) A 18.90 (5.75) 17.34 97.29 (91.48–103.47) B 19.47 (6.08) 17.82 ‐ ‐ C max (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