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This Article Full Text Full Text (PDF) All Versions of this Article: 0091270009334377v1 0091270009334377v2 49/11/1363    most recent 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Google Scholar Articles by Haroutiunian, S. Articles by Hoffman, A. PubMed PubMed Citation Articles by Haroutiunian, S. Articles by Hoffman, A. Social Bookmarking                         What's this?

Valproic Acid Plasma Concentration Decreases in a Dose-Independent Manner Following Administration of Meropenem: A Retrospective Study

From the Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (Mr Haroutiunian, Ms Ratz, Dr Hoffman) and Pharmacy Services, Sheba Medical Center, Tel Hashomer, Israel (Ms Rabinovich, Ms Adam).

Several case reports indicate that carbapenem antibiotics, especially meropenem, may decrease the plasma concentrations of valproic acid (VPA), thus decreasing its therapeutic activity. To investigate the onset, severity, and dose dependency of the interaction between meropenem and VPA, the authors carried out a retrospective evaluation of data collected during 24 months from patients hospitalized in a tertiary medical center. The analysis included 36 patients. VPA mean ± SEM plasma concentration decreased from of 50.8 ± 4.5 µg/mL to 9.9 ± 2.1 µg/mL (P < .001) following meropenem administration. After discontinuation of meropenem, VPA plasma concentrations remained low for 7 days and then gradually increased after 8 to 14 days, reaching values comparable to those before meropenem initiation. Different daily VPA doses showed a similar pattern of decreased VPA concentrations. The mean decrease in individual plasma VPA concentration was 82.1% ± 2.7%. The mean VPA plasma concentration of patients in whom samples were drawn within 24 hours of meropenem initiation was 9.9 ± 3.2 µg/mL. In conclusion, the interaction between meropenem and VPA causes a significant decrease in VPA plasma concentration, apparently within 24 hours. As the therapeutic effects of VPA are plasma concentration dependent, the data suggest that these drugs should not be administered concomitantly.

Key Words: Meropenem • valproic acid • drug-drug interaction • epilepsy • pharmacokinetics

Address for reprints: Amnon Hoffman, PhD, Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, PO Box 12065, Jerusalem 91120, Israel; e-mail: amnonh{at}ekmd.huji.ac.il.

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