The maximum plasma concentration following chronic administration at the recommended dose of 5 mg twice daily is 22 ng/mL (CV=29%). The intake of the tablet during meals is recommended in order to decrease infra-individual variability in exposure.ĭistribution: Ivabradine is approximately 70% plasma protein bound and the volume of distribution at steady state is close to 100 L in patients. The absolute bioavailability of the film-coated tablets is around 40%, due to first-pass effect in the gut and liver.įood delayed absorption by approximately 1 hour, and increased plasma exposure by 20 to 30 %. The N-desmethylated derivative of ivabradine has been identified as the main active metabolite in humans.Ībsorption and bioavailability: Ivabradine is rapidly and almost completely absorbed after oral administration with a peak plasma level reached in about 1 hour under fasting condition. Ivabradine is the S-enantiomer with no bioconversion demonstrated in vivo. Ivabradine: Under physiological conditions, ivabradine is rapidly released from tablets and is highly water-soluble (>10 mg/mL). Pharmacokinetics: The rate and extent of absorption of ivabradine and metoprolol from Implicor are not significantly different, respectively, from the rate and extent of absorption of ivabradine and metoprolol when taken alone as monotherapy. It also reduces the rise in blood pressure due to exertion. Metoprolol has an antihypertensive effect, both in the orthostatic and supine position. Metoprolol: Metoprolol reduces or inhibits the catecholamines effect on the heart, which leads to a decrease in the rhythm, contractility and cardiac output. Ivabradine does not influence intracardiac conduction, contractility (no negative inotropic effect) or ventricular repolarizatlon: In clinical electrophysiology studies, ivabradine had no effect on atrioventricular or intraventricular conduction times or corrected QT intervals in patients with left ventricular dysfunction (left ventricular ejection fraction (LVEF) between 30 and 45%), ivabradine did not have any deleterious influence on LVEF. This leads to a reduction in cardiac workload and myocardial oxygen consumption. At usual recommended doses, heart rate reduction is approximately 10 bpm at rest and during exercise. Analysis of heart rate reduction with doses up to 20 mg twice daily indicates a trend towards a plateau effect which is consistent with a reduced risk of severe bradycardia below 40 bpm. Pharmacology: Pharmacodynamics: Ivabradine: The main pharmacodynamic property of ivabradine in humans is a specific dose dependent reduction in heart rate.

Half life of metoprolol