HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Jerling, M. Articles by Hussein, Z. Search for Related Content PubMed PubMed Citation Articles by Jerling, M. Articles by Hussein, Z. Social Bookmarking                         What's this?

Studies to Investigate the Pharmacokinetic Interactions Between Ranolazine and Ketoconazole, Diltiazem, or Simvastatin During Combined Administration in Healthy Subjects

From CV Therapeutics Inc, Palo Alto, California (Dr Jerling, B.-L. Huan, Dr Leung, N. Chu, Dr Abdallah), and Medeval Ltd, Manchester, United Kingdom (Dr Hussein).

The interactions of ranolazine, a new antianginal compound, with inhibitors and substrates of the CYP3A isoenzyme family were studied in 1 open-label and 4 double-blind, randomized, multiple-dose studies. In healthy adult volunteers, the authors sought (1) to determine the steady-state pharmacokinetics, safety, and tolerability of immediate- and sustained-release ranolazine with and without ketoconazole, diltiazem, or simvastatin and (2) to evaluate the effect of ranolazine on the pharmacokinetics of diltiazem, simvastatin, simvastatin metabolites, and HMG-CoA reductase activity. Ketoconazole increased ranolazine plasma concentrations and reduced the CYP3A4-mediated metabolic transformation of ranolazine, confirming that CYP3A4 is the primary metabolic pathway for ranolazine. Diltiazem reduced oral clearance of ranolazine in a dose-dependent manner. Simvastatin did not affect ranolazine pharmacokinetics, although ranolazine increased the AUC and C_max of simvastatin, simvastatin acid, 2 simvastatin metabolites, and HMG-CoA reductase activity by <2-fold. Administration of ranolazine in combination with diltiazem or simvastatin was safe and well tolerated during the interval studied.

Key Words: Ranolazine • ketoconazole • diltiazem • simvastatin • drug interactions

Address for reprints: Markus Jerling, MD, PhD, CV Therapeutics Inc, 3172 Porter Drive, Palo Alto, CA 94304.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. Zhao, C. A. Lee, and K. L. Kunze Sequential Metabolism Is Responsible for Diltiazem-Induced Time-Dependent Loss of CYP3A Drug Metab. Dispos., May 1, 2007; 35(5): 704 - 712. [Abstract] [Full Text] [PDF]

				K. Zerumsky and B. F. McBride Ranolazine in the management of chronic stable angina Am. J. Health Syst. Pharm., December 1, 2006; 63(23): 2331 - 2338. [Abstract] [Full Text] [PDF]

				T. Shimizu, K. Akimoto, T. Yoshimura, T. Niwa, K. Kobayashi, M. Tsunoo, and K. Chiba AUTOINDUCTION OF MKC-963 [(R)-1-(1-CYCLOHEXYLETHYLAMINO)-4-PHENYLPHTHALAZINE] METABOLISM IN HEALTHY VOLUNTEERS AND ITS RETROSPECTIVE EVALUATION USING PRIMARY HUMAN HEPATOCYTES AND CDNA-EXPRESSED ENZYMES Drug Metab. Dispos., June 1, 2006; 34(6): 950 - 954. [Abstract] [Full Text] [PDF]

				B. R. Chaitman Ranolazine for the Treatment of Chronic Angina and Potential Use in Other Cardiovascular Conditions Circulation, May 23, 2006; 113(20): 2462 - 2472. [Full Text] [PDF]

				M. J Tafreshi and E. Fisher Ranolazine: A New Approach to Management of Patients with Angina Ann. Pharmacother., April 1, 2006; 40(4): 689 - 693. [Abstract] [Full Text] [PDF]