Zibotentan Can Be Co-administered with Contraceptives Containing Ethinyl Estradiol and Levonorgestrel: A Pharmacokinetic Drug-Drug Interaction Study.
Autor: | Mercier AK; Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden., Kois AK; Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gaithersburg, Maryland, USA., Karsanji D; Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Baldry R; Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Birve F; Biometrics, Late-Stage Development, Cardiovascular, Renal and Metabolism, R&D, AstraZeneca, Gothenburg, Sweden., Hedwall M; Clinical, Late-Stage Development, Cardiovascular, Renal and Metabolism, R&D, AstraZeneca, Gothenburg, Sweden., Molodetskyi O; Global Patient Safety BioPharmaceuticals, Chief Medical Office, R&D, AstraZeneca, Gothenburg, Sweden., Gillen M; Creek Lane PK, LLC, Waterford, Virginia, USA. |
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Jazyk: | angličtina |
Zdroj: | Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2024 Aug; Vol. 116 (2), pp. 372-379. Date of Electronic Publication: 2024 Apr 30. |
DOI: | 10.1002/cpt.3280 |
Abstrakt: | The endothelin A receptor antagonist zibotentan, combined with the sodium-glucose co-transporter-2 inhibitor dapagliflozin, is being investigated for the treatment of chronic kidney disease with high proteinuria. To allow women of childbearing potential access to this treatment, highly effective contraception is required and drug interactions compromising contraception reliability must be avoided. This study investigated the risk of pharmacokinetic (PK) interaction between zibotentan and the contraceptives ethinyl estradiol and levonorgestrel. A single-sequence, within-participant comparison study was conducted in 24 healthy women of non-childbearing potential, comparing the PK of ethinyl estradiol/levonorgestrel alone and with zibotentan. Single oral doses of 0.06 mg ethinyl estradiol/0.3 mg levonorgestrel were administered on Days 1 and 15; zibotentan 10 mg was dosed orally, once-daily through Days 6-19. PK profiles were determined and ethinyl estradiol/levonorgestrel PK was compared between Day 1 and 15 based on geometric least-squares mean ratios of PK parameters, including maximum observed concentration (C (© 2024 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.) |
Databáze: | MEDLINE |
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