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 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 Google Scholar Google Scholar Articles by Greenblatt, D. J. Articles by Zinny, M. A. Search for Related Content PubMed PubMed Citation Articles by Greenblatt, D. J. Articles by Zinny, M. A. Social Bookmarking                         What's this?

Clonazepam Pharmacokinetics: Comparison of Subcutaneous Microsphere Injection With Multiple-Dose Oral Administration

From the Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts-New England Medical Center, Boston, Massachusetts (D. J. Greenblatt, J. S. Harmatz, G. Chen); Biotek, Inc., Woburn, Massachusetts (P. D. Blaskovich, E. S. Nuwayser); and ProMedica Clinical Research Center, Boston, Massachusetts (M. A. Zinny).

Nine healthy volunteers participated in a 3-phase clinical pharmacokinetic study of the benzodiazepine derivative clonazepam. During phases I and II, subjects received the conventional oral dosage form of clonazepam, 0.5 mg 3 times daily, for 7 days. Multiple plasma samples were drawn on day 1 and day 7 of the trial and once daily during the washout period after the final dose. Based on nonlinear regression, mean kinetic variables for clonazepam were: absorption half-life, 24 minutes; elimination half-life, 40 hours; apparent oral clearance, 72 mL/min. The extent of accumulation at steady state relative to the first day of treatment averaged 3.3-fold, and was consistent with values predicted based on the elimination half-life. This finding suggests that once-daily dosage with clonazepam would be appropriate for many patients. In phase III of the study, subjects received a single 2.7 mg subcutaneous injection of a microsphere formulation of clonazepam, designed to produce a sustained-release profile. The maximum average plasma clonazepam concentration was 3.0 ng/mL, reached at 72 hours after dosage. Thereafter, plasma concentrations fell slowly over the 13-day sampling period, remaining above 1 ng/mL for 12 days. Overall systemic availability of clonazepam from the microsphere injection, relative to the conventional oral dosage form, was 1.05. Thus, the microsphere preparation of injectable clonazepam provides complete absorption from the injection site, with the intended slow-release pharmacokinetic profile.

Key Words: Clonazepam • benzodiazepines • pharmacokinetics • microspheres

Address for reprints: David J. Greenblatt, MD, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111.

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