Lack of interaction between orlistat and oral contraceptives.
OBJECTIVE
Orlistat, a potent and selective inhibitor of gastrointestinal lipases, is designed for the treatment of obesity. A double-blind, randomised, placebo-controlled, 2-way crossover study investigated the possible influence of orlistat on the ovulation-suppressing action of combination oral contraceptives (OC).


METHODS
After an 8-day run-in prior to the first of two consecutive menstrual cycles (Day 1 was the first day of menstruation), two groups of 10 healthy women, 20-27 years of age and on a stable regimen with OCs, received either 120 mg orlistat t.i.d. or placebo t.i.d. on Days 1-23 of the first cycle, and, separated by a placebo washout period on Days 24-28, the alternative treatment on Days 1-23 of the second cycle. In both cycles, serum luteinizing hormone (LH) was measured on Days 12-16 and progesterone on Days 12, 16, 19-23.


RESULTS
The geometric means of time averaged concentrations (Days 12-16 for LH and Days 19-23 for progesterone) in the cycles with orlistat and placebo, respectively, and the one-sided 95% confidence region for the mean in the cycle with orlistat were 1.92, 2.03 and < 2.23 IU 1-1 for LH and 0.147, 0.145 and < 0.176 micrograms 1-1 for progesterone. The one-sided 95% confidence region for the ratio (orlistat/placebo) of geometric means was < 1.06 for LH and < 1.11 for progesterone.


CONCLUSIONS
During normal ovulation the peak serum concentration of LH is above 30 IU 1-1 around Day 14 of the cycle, and that of progesterone exceeds 3 micrograms 1-1 around Day 21. The 95% confidence regions for the means, as well as all individual concentrations, were below these limits. It was concluded that orlistat did not influence the ovulation suppressing action of oral contraceptives.
Hartmann
D
D
Department of Clinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Güzelhan
C
C
Zuiderwijk
P B
PB
Odink
J
J
D000328:Adult; D000704:Analysis of Variance; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007783:Lactones / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D000077403:Orlistat; D011374:Progesterone / Q000097:blood; D011863:Radioimmunoassay
D003277:Contraceptives, Oral, Combined; D004791:Enzyme Inhibitors; D007783:Lactones; D011374:Progesterone; D007986:Luteinizing Hormone; D000077403:Orlistat