title: Pharmacokinetic interactions of OBE001 and betamethasone in healthy female volunteers.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: ObsEva SA, Plan-les-Ouates, Geneva, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Pohl
authors.forename: M-C
authors.initials: MC
authors.lastname: Homery
authors.forename: F
authors.initials: F
authors.lastname: Lemaux
authors.forename: A
authors.initials: A
authors.lastname: Patat
authors.forename: A
authors.initials: A
authors.lastname: Chollet
mesh_terms: D019540:Area Under Curve; D001623:Betamethasone / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged; D010091:Oximes / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D015149:Tocolytic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; C000604229:OBE001; D010091:Oximes; D011759:Pyrrolidines; D015149:Tocolytic Agents; D001623:Betamethasone
keywords: OBE001; corticosteroid; drug interaction; pharmacokinetic; preterm labour