Valproic acid plasma concentration decreases in a dose-independent manner following administration of meropenem: A retrospective study

Simon Haroutiunian, Bella Rabinovich, Miriam Adam, Amnon Hoffman, Yael Ratz

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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 ?μ g/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 μ g/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.

Original languageEnglish
Pages (from-to)1363-1369
Number of pages7
JournalJournal of clinical pharmacology
Volume49
Issue number11
DOIs
StatePublished - Nov 1 2009

Keywords

  • Drug-drug interaction
  • Epilepsy
  • Meropenem
  • Pharmacokinetics
  • Valproic acid

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