Investigation of Possible Pharmacokinetic Interaction Between Ivabradine and Carvedilol in Rats using High Performance Liquid Chromatography/Mass Spectroscopy
Saif S. Abbas1, Israa H. Al-Ani1, Wael A. Abu Dayyih2, Ghaleb Oriquat1 and Samira F. Hassan1

1Al-Ahliyya Amman University, Amman, Jordan.

2University of Petra, Amman, Jordan.

Corresponding Author E-mail:

Abstract: Ivabradine is a new hyperpolarization-activated cyclic nucleotide-gated channel (HCN) blocker. It has been approved by the FDA in 2015 as a part of management of stable angina and congestive heart failure. The aim of this study was to investigate the possibility of pharmacokinetic interaction of a proposed combination of ivabradine and the β- blocker carvedilol in rats using spectroscopy technique. A simple, rapid and sensitive method for validation and determination of ivabradine and carvedilol in the rats’ plasma was developed using HPLC/MS. The method was successfully developed and validated in terms of linearity, precision and accuracy which were within the values accepted by European Medical Agency and International Conference of Harmonization guidlines. Ivabradine and Carvedilol were given both intravenously and orally each alone and as oral combination to fasted Sprague- Dawley rats. Blood samples were withdrawn on scheduled time intervals up to 36 hours and analyzed for each drug. Results showed significant increase in bioavailability of both drugs in combination specially on elimination level  expressed in decrease clearance and  increase in the  half-life for both drugs. In conclusion, a significant kinetic interaction occurred when ivabradine  was given orally with carvedilol which makes dose adjustment of both drugs of much importance.

Keywords: Ivabradine; Carvedilol; Pharmacokinetic Interaction; HPLC/MS

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