Pharmacokinetic interactions of OBE001 and betamethasone in healthy female volunteers.

What Is Known And Objective: To treat preterm labour, antenatal corticosteroids and tocolytics are often co-administered. OBE001 is an orally active oxytocin receptor antagonist under development for preterm labour treatment.

Methods: Co-administration of OBE001 and betamethasone to determine pharmacokinetic interactions was studied during an open-label, randomized, three-period crossover study. Twelve healthy post-menopausal volunteers received either two consecutive OBE001 administrations of 600 mg/day, two intramuscular injections of 12 mg/day betamethasone or the two drugs administered in combination. The area under the plasma concentration-time curve (AUC), the maximum plasma concentration (Cmax) and the time to Cmax (tmax) for OBE001 and betamethasone were measured.

Results And Discussion: There was no effect on geometric mean Cmax after the second administration and AUCs of OBE001 [geometric mean ratio point estimate (90% CI): Cmax (Day2) 1·05 (0·98-1·12) and AUC(0-24 h )1·11 (0·99-1·23)/AUC(24 h-∞) 0·99 (0·93-1·06), respectively]; Cmax after the first administration together with betamethasone was increased by 12% [geometric mean ratio point estimates (90% CI): Cmax (Day1) 1·12 (0·96-1·32)]. Tmax after concomitant administration with betamethasone occurred with a median delay of 1 h. Geometric mean Cmax and AUCs of betamethasone were not affected by concomitant OBE001 administration [geometric mean ratio point estimate (90% CI): Cmax (Day1) 1·02 (0·98-1·07)/Cmax (Day2) 1·03 (0·98-1·08) and AUC(0-24 h) 1·07 (1·04-1·11)/AUC(24 h-∞ )1·04 (1·01-1·08), respectively], with no effect on median tmax . No subject was discontinued from the study due to adverse events.

What Is New And Conclusion: AUC and Cmax of the betamethasone and OBE001 combination did not differ significantly between treatments. Co-administration of OBE001 and betamethasone was well tolerated and resulted in a tmax median delay of 1 h for OBE001 but not for betamethasone. Co-administration of OBE001 and betamethasone in clinics is feasible and does not require any specific precaution or administration adaptation.