Effect of mavoglurant (AFQ056), a selective mGluR5 antagonist, on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women

• Published in: International journal of clinical pharmacology and therapeutics Vol. 53; no. 7; pp. 550 - 556
• Main Authors: Sivasubramanian, Rama, Chakraborty, Abhijit, Rouzade-Dominguez, Marie-Laure, Neelakantham, Srikanth, Jakab, Annamaria, Mensinga, Tjeert, Legangneux, Eric, Woessner, Ralph, Ufer, Mike
• Format: Journal Article
• Language: English
• Published: Germany 01-07-2015
• Subjects: Administration, Oral; Adolescent; Adult; Area Under Curve; Contraceptives, Oral, Combined - administration & dosage; Contraceptives, Oral, Combined - adverse effects; Contraceptives, Oral, Combined - blood; Contraceptives, Oral, Combined - pharmacokinetics; Contraceptives, Oral, Hormonal - administration & dosage; Contraceptives, Oral, Hormonal - adverse effects; Contraceptives, Oral, Hormonal - blood; Contraceptives, Oral, Hormonal - pharmacokinetics; Drug Interactions; Ethinyl Estradiol - administration & dosage; Ethinyl Estradiol - adverse effects; Ethinyl Estradiol - blood; Ethinyl Estradiol - pharmacokinetics; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - adverse effects; Female; Healthy Volunteers; Humans; Indoles - administration & dosage; Indoles - adverse effects; Levonorgestrel - administration & dosage; Levonorgestrel - adverse effects; Levonorgestrel - blood; Levonorgestrel - pharmacokinetics; Metabolic Clearance Rate; Models, Biological; Receptor, Metabotropic Glutamate 5 - antagonists & inhibitors; Young Adult
• ISSN: 0946-1965
• DOI: 10.5414/CP202321

To compare the pharmacokinetics (PKs) of a combination oral contraceptive (OC) when given alone or concomitantly with the selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056).
This open-label, fixed-sequence, two-period study included 30 healthy female subjects aged 18-40 years. In period 1, a single oral dose of an OC containing 30 μg ethinyl estradiol (EE)/150 μg levonorgestrel (LNG) was administered alone. In period 2, the OC was administered with a clinically relevant multiple dose of mavoglurant 100 mg b.i.d. under steady-state conditions. Plasma concentrations of EE and LNG were measured up to 72 hours post administration, and the PK parameters Cmax and AUClast were estimated using noncompartmental methods.
The geometric mean ratios of EE Cmax and AUClast obtained with and without mavoglurant were 0.97 (90% confidence interval (CI): 0.90-1.06) and 0.94 (90% CI: 0.86-1.03), respectively. The corresponding Cmax and AUClast for LNG were 0.81 (90% CI: 0.75-0.87) and 0.68 (90% CI: 0.63-0.73), respectively.
In conclusion, EE PK was unchanged, whereas Cmax and AUClast of LNG were 19% and 32% lower, respectively, when given with mavoglurant Further investigation regarding the impact on contraceptive efficacy is warranted.