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Coadministration of the prostaglandin F2α receptor antagonist preterm labour drug candidate OBE022 with magnesium sulfate, atosiban, nifedipine and betamethasone.
Pohl, Oliver; Marchand, Line; Gotteland, Jean-Pierre; Coates, Simon; Täubel, Jörg; Lorch, Ulrike.
Afiliación
  • Pohl O; ObsEva SA, 1228, Plan-les-Ouates, Switzerland.
  • Marchand L; ObsEva SA, 1228, Plan-les-Ouates, Switzerland.
  • Gotteland JP; ObsEva SA, 1228, Plan-les-Ouates, Switzerland.
  • Coates S; Richmond Pharmacology, St. George's University London, UK.
  • Täubel J; Richmond Pharmacology, St. George's University London, UK.
  • Lorch U; St. George's University London, UK.
Br J Clin Pharmacol ; 85(7): 1516-1527, 2019 07.
Article en En | MEDLINE | ID: mdl-30891820
AIMS: To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development. METHODS: Part A: open-label, randomized, 3-period crossover assessing coadministration of single doses of OBE022 (1100 mg) and MgSO4 . Part B: open-label, single-sequence crossover assessing the interactions following administration of OBE022 (1000 mg/day) at steady state coadministered with single doses of atosiban, nifedipine and betamethasone. Twenty-five healthy nonpregnant women of reproductive age were enrolled (Part A: n = 12; Part B: n = 13). RESULTS: OBE022, alone or in combination with standard-of-care medications, was well tolerated. Headache and dizziness were the most frequently reported adverse events; dizziness occurred more often with the nifedipine/OBE022 combination. There were no clinically significant pharmacokinetic interactions when coadministered with MgSO4 . Co-administration had no notable effect on atosiban exposure. Atosiban reduced exposure to OBE002 (peak concentration [Cmax ] 22%, area under the concentration-time curve [AUC] 19%). Coadministration with betamethasone slightly increased betamethasone exposure (Cmax  + 18%, AUC +27%) and OBE002 exposure (Cmax  + 35%, AUC +15%). These changes were not considered clinically significant. Coadministration with nifedipine slightly increased OBE002 exposure (Cmax  + 29%, AUC +24%) and markedly increased nifedipine exposure (Cmax by 2-fold and AUC by 2-fold), which may be clinically significant. CONCLUSIONS: The use of OBE022, a PGF2α antagonist prodrug, in combination with standard-of-care medicines may provide new treatment alternatives for preterm labour. All tested combinations were well tolerated. Nifedipine doses could potentially be reduced or staggered when coadministered with OBE022.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sulfonas / Tocolíticos / Ésteres / Tiazolidinas Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adolescent / Adult / Female / Humans / Middle aged Idioma: En Revista: Br J Clin Pharmacol Año: 2019 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sulfonas / Tocolíticos / Ésteres / Tiazolidinas Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adolescent / Adult / Female / Humans / Middle aged Idioma: En Revista: Br J Clin Pharmacol Año: 2019 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido