The effect of laquinimod, a novel immuno-modulator in development to treat Huntington disease, on the pharmacokinetics of ethinylestradiol and levonorgestrel in healthy young women
| Autor: | Spiegelstein O, Zur Aa, Mimrod D, Bar-Ilan O, Dror, Korver T, Anna Elgart |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Adolescent Cmax Administration Oral Levonorgestrel Quinolones Pharmacology Bioequivalence Ethinyl Estradiol 030226 pharmacology & pharmacy Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Double-Blind Method Pharmacokinetics Ethinylestradiol medicine Humans Immunologic Factors Drug Interactions Pharmacology (medical) 030212 general & internal medicine Adverse effect Cross-Over Studies business.industry Headache General Medicine Crossover study Contraceptives Oral Combined Drug Combinations Therapeutic Equivalency chemistry Area Under Curve Female business Laquinimod medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 75:41-49 |
| ISSN: | 1432-1041 0031-6970 |
| DOI: | 10.1007/s00228-018-2549-7 |
| Popis: | Laquinimod is an orally dosed immuno-modulator currently under development for Huntington’s disease (HD). Preclinical findings suggest potential teratogenicity of laquinimod, thus the reproductive ability of females with HD treated with laquinimod needs to be closely managed. Because combined oral contraceptives (COC) are often used in this context, the pharmacokinetics of COC containing ethinylestradiol (EE) and levonorgestrel (LNG) in combination with laquinimod (0.6 mg/day) was evaluated. In this randomized, phase-1 single-center, double-blind, placebo-controlled, 2-way crossover drug-drug interaction (DDI) study in 48 healthy premenopausal women, COC were administered in a 28-day regimen of 21 days followed by 7 pill-free days for 4 cycles and laquinimod or placebo was administered for 28 days in cycle 1 and cycle 3 starting 7 days prior to COC administration. Blood samples for pharmacokinetic profiling of laquinimod, EE and LNG were collected on day 21 and day 22 of Cycles 1 and 3 pre-dose and multiple times post-dose. The ratio of geometric means and 90% confidence intervals for AUC0-24 and Cmax of EE and LNG with and without laquinimod were all within the bioequivalence range (80 to 125%). Laquinimod pharmacokinetics was consistent with those observed in previous studies. The adverse event profile was in line with the current knowledge on the safety profile of both drugs, with headache as the most frequently reported treatment-related adverse event. The combination of COC and laquinimod treatment was found to be safe, tolerable, and devoid of any noticeable pharmacokinetic interaction. |
| Databáze: | OpenAIRE |
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