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Pharmacokinetic interactions of OBE 001 and betamethasone in healthy female volunteers
Author(s) -
Pohl O.,
Homery M.C.,
Lemaux F.,
Patat A.,
Chollet A.
Publication year - 2015
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12258
Subject(s) - cmax , betamethasone , pharmacokinetics , medicine , crossover study , geometric mean , area under the curve , pharmacology , placebo , mathematics , statistics , alternative medicine , pathology
Summary What is known and objective To treat preterm labour, antenatal corticosteroids and tocolytics are often co‐administered. OBE 001 is an orally active oxytocin receptor antagonist under development for preterm labour treatment. Methods Co‐administration of OBE 001 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 OBE 001 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 (C max ) and the time to C max (t max ) for OBE 001 and betamethasone were measured. Results and discussion There was no effect on geometric mean C max after the second administration and AUC s of OBE 001 [geometric mean ratio point estimate (90% CI ): C max 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]; C max after the first administration together with betamethasone was increased by 12% [geometric mean ratio point estimates (90% CI ): C max Day1 1·12 (0·96–1·32)]. T max after concomitant administration with betamethasone occurred with a median delay of 1 h. Geometric mean C max and AUC s of betamethasone were not affected by concomitant OBE 001 administration [geometric mean ratio point estimate (90% CI ): C max Day1 1·02 (0·98–1·07)/C max 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 t max . No subject was discontinued from the study due to adverse events. What is new and conclusion AUC and C max of the betamethasone and OBE 001 combination did not differ significantly between treatments. Co‐administration of OBE 001 and betamethasone was well tolerated and resulted in a t max median delay of 1 h for OBE 001 but not for betamethasone. Co‐administration of OBE 001 and betamethasone in clinics is feasible and does not require any specific precaution or administration adaptation.