PD14-01 ONCE-DAILY VIBEGRON, A NOVEL ORAL &bgr;3 AGONIST DOES NOT INHIBIT CYP2D6, A COMMON PATHWAY FOR DRUG METABOLISM IN PATIENTS ON OAB MEDICATIONS
Abstract
INTRODUCTION AND OBJECTIVES: Vibegron is a selective &bgr;3-adrenergic receptor agonist in development for overactive bladder (OAB). Approximately 43% of patients on any OAB medication are taking a drug metabolized through the CYP2D6 pathway. In vitro data (human liver microsomal incubations and hepatocyte cultures) demonstrate that vibegron at concentrations up to 100 &mgr;M does not inhibit human cytochrome P450 (CYP) enzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Two clinical studies were conducted to evaluate the pharmacokinetic, safety, and tolerability effects of vibegron on the CYP2D6 substrates tolterodine and metoprolol in healthy volunteers. METHODS: Two phase-1, single-center, open-label studies enrolled healthy volunteers to receive multiple-dose tolterodine extended release (ER) 4 mg with and/or without multiple doses of vibegron 100 mg (n=12), or single-dose metoprolol succinate 100 mg with and without multiple-dose vibegron 75 mg (n=24). Pharmacokinetic parameters were calculated to evaluate tolterodine or metoprolol alone and in combination with steady-state vibegron. Safety and tolerability were assessed throughout the study. RESULTS: Coadministration of vibegron did not alter the geometric mean maximum plasma concentration (Cmax) and the area under the curve (AUC) of tolterodine (geometric mean ratio [90% confidence intervals], 1.12 [1.00, 1.26] and 1.08 [0.97, 1.21]), respectively. The elimination half-life of tolterodine was similar…
Read the paper
Related studies
- Sarcopenia, sarcopenic overweight/obesity and risk of cardiovascular disease and cardiac arrhythmia: A cross-sectional study
- Workplace Violence Is Associated With Impaired Work Functioning in Nurses: An Italian Cross-Sectional Study
- Vagus Nerve Dysfunction in the Post-COVID-19 Condition: a pilot cross sectional study
- Association Between Metabolic Associated Fatty Liver Disease and Chronic Kidney Disease: A Cross-Sectional Study from NHANES 2017–2018
- Efficacy and safety of solifenacin succinate 10 mg once Daily: A multicenter, phase III, randomized, double-blind, placebo-controlled, parallel-group trial in patients with overactive bladder
- Association between triglyceride glucose‐body mass index and hypertension in Chinese adults: A cross‐sectional study
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.