Effects of ponesimod, a selective S1P1 receptor modulator, on the pharmacokinetics of a hormonal combination contraceptive.

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Reyes M, Brossard P, Chassard D, Hoch M, Dingemanse J

Effects of ponesimod, a selective S1P1 receptor modulator, on the pharmacokinetics of a hormonal combination contraceptive.

Eur J Clin Pharmacol. 2014 Mar;70(3):287-93. doi: 10.1007/s00228-013-1625-2. Epub 2013 Dec 22.

PubMed ID

24362488 [ View in PubMed

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Abstract

PURPOSE: To determine the effects of steady-state concentrations of the selective S1P1 receptor modulator ponesimod on the pharmacokinetics (PK) of a single dose of a combined oral contraceptive, containing 1 mg norethisterone (NET) and 35 mug ethinyl estradiol (EE) and to investigate the effects on heart rate at different ponesimod doses within an up-titration regimen prior to co-administration of the contraceptive. METHODS: Twenty-two healthy women (age: 29-60 years) received twice a single oral dose of the combined oral contraceptive, alone or in combination with multiple doses of 40 mg ponesimod attained by an up-titration regimen. Heart rate (HR) effects were assessed on the first day of each up-titration level. PK parameters of NET and EE were determined by non-compartmental analysis. RESULTS: Geometric mean ratios (ponesimod and contraceptive / contraceptive alone) of Cmax and AUC0-24 of NET were 0.87 (90 % CI: 0.80, 0.94) and 0.84 (90 % CI: 0.76, 0.93), respectively. Geometric mean ratios of Cmax and AUC0-24 of EE were 0.94 (90 % CI: 0.86, 1.03) and 0.95 (90 % CI: 0.89, 1.01), respectively. The maximum mean HR reduction after the first dose of 10 mg ponesimod was 12.4 bpm (SD +/- 6.2) at 2.5 h post-dose. On Day 4 (first dose of 20 mg) and Day 7 (first dose of 40 mg) the maximum mean HR reduction was 4.3 bpm (SD +/- 5.7) and 1.4 (SD +/- 6.4), respectively, at 2.5 h post-dose compared to baseline. CONCLUSION: No clinically relevant PK interactions between ponesimod and the combined oral contraceptive were observed, therefore, efficacy of hormonal contraceptives is not expected to be affected by concomitant administration of ponesimod. The up-titration regimen showed that HR reductions are diminished upon repeated ponesimod administration.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ponesimod	Sphingosine 1-phosphate receptor 1	Protein	Humans	Yes	Agonist Modulator Regulator	Details