The Effect of Carbapenem Antibiotics on Plasma Concentrations of Valproic Acid

@article{Mancl2009TheEO,
  title={The Effect of Carbapenem Antibiotics on Plasma Concentrations of Valproic Acid},
  author={Erin E Mancl and Barry E. Gidal},
  journal={Annals of Pharmacotherapy},
  year={2009},
  volume={43},
  pages={2082 - 2087}
}
  • E. Mancl, B. Gidal
  • Published 1 December 2009
  • Chemistry, Medicine
  • Annals of Pharmacotherapy
Objective: To critically evaluate the mechanisms of the interaction between valproic acid and carbapenem antibiotics. Data Sources: A PubMed search (January 1971–June 2009) was performed to identify literature on the interaction between valproic acid and carbapenem antibiotics. Additional references were identified through review of bibliographies of identified articles. Study Selection and Data Extraction: Data on the mechanisms of the interaction between valproic acid and carbapenem… 
Reduced Valproic Acid Serum Concentrations Due to Drug Interactions With Carbapenem Antibiotics: Overview of 6 Cases
TLDR
The interaction between VPA and carbapenem antibiotics caused decreases in the VPA serum concentrations; the extent of this decrease was greater in the meropenem-treated patients than in the imipenem- treated or ertapenen-treated cases.
Effect of drug interactions between carbapenems and valproate on serum valproate concentration: a systematic review and meta-analysis
TLDR
The drug interaction between valproate and carbapenem causes substantial SVC decreases, even to subtherapeutic levels, which may increase the risk of seizures.
The role of the hepatic metabolisation for the interaction between valproic acid and carbapenem antibiotics
TLDR
The authors conclude that this time course suggests that mechanisms other than a change in the enzymatic elimination of VPA are the cause for the pharmacokinetic interaction.
Interaction between valproic acid and carbapenems: Case series and literature review
TLDR
Clinicians should be aware of this potential interaction and closely monitor serum VPA levels and possible failure to control seizures with the concomitant use of carbapenems.
Interaction between valproic acid and carbapenems: Case series and literature review
Several case reports and retrospective studies have indicated that carbapenems decrease the serum concentration of valproic acid (VPA), thus decreasing its therapeutic activity. This study evaluates
[Analysis of the valproic acid-meropenem interaction in hospitalised patients].
TLDR
The interaction between valproic acid and meropenem is serious and the concomitant use of both drugs should be avoided, replacing the antibiotherapy empirically, or according to the resistance profiles of the microorganism and maintaining the same the anti-epileptic treatment.
The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations
TLDR
The extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem was compared and concomitant use of VPA and CBPMs should be avoided.
Concomitant treatment with imipenem causes a rapid and extensive decrease in the plasma concentrations of valproic acid
Background. Valproic acid (VPA) is a wide-spectrum antiepileptic drug used both in children and in adults. We describe a clinically important interaction between VPA and imipenem, a carbapenem
Drug interaction between valproic acid and carbapenems in patients with epileptic seizures
TLDR
Clinicians need to be aware of the reduction of VPA concentrations to subtherapeutic levels and the aggravation of seizures while patients are treated with a combination of carbapenems and VPA, according to this study.
Interactions between carbapenems and valproic acid among the patients in the intensive care units.
TLDR
Carapenems decreased VPA serum concentration and increased the risk of epileptic seizures and SE, which led to increased length of ICU stay in patients concomitantly receiving VPA and carbapenem.
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References

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Inhibition by carbapenem antibiotic imipenem of intestinal absorption of valproic acid in rats
TLDR
Imipenem inhibits the intestinal absorption of valproic acid, which contributes to the decrease in plasma concentration of valProic acid after oral administration, which is caused by a mechanism different from that of lactic acid.
Carbapenem antibiotics inhibit valproic acid transport in Caco-2 cell monolayers.
TLDR
The carbapenems may inhibit the absorption of valProic acid at the basolateral membrane of intestinal epithelial cells, which contributes to the decrease in plasma concentration of valproic acid after oral administration.
Increased erythrocyte distribution of valproic acid in pharmacokinetic interaction with carbapenem antibiotics in rat and human.
TLDR
The pharmacokinetic interaction between VPA and carbapenem antibiotics, in which plasma VPA levels were markedly reduced, may partly be derived from the increased erythrocyte distribution of VPA.
MECHANISM OF THE DRUG INTERACTION BETWEEN VALPROIC ACID AND CARBAPENEM ANTIBIOTICS IN MONKEYS AND RATS
TLDR
Results clearly indicate one of the important causes of drug interaction as follows: carbapenems would inhibit the hydrolytic enzyme, which is involved in the Hydrolysis of VPA-G to VPA, resulting in a decrease of plasma concentration of V PA.
Interaction of valproic acid and carbapenem antibiotics with multidrug resistance-associated proteins in rat erythrocyte membranes
TLDR
Results indicate that VPA and CPs interact with Mrp-mediated transport in erythrocyte membranes, and VPA itself is transported by Mrps, which is inhibited by panipenem.
Meropenem decreases serum level of valproic acid.
TLDR
It is clear that concomitant meropenem administration decreases serum valproic acid concentration, and it is believed that there may be no need to change the antiepileptic drug during this period, provided that the patient has no seizure.
Effect of Meropenem on Disposition Kinetics of Valproate and Its Metabolites in Rabbits
TLDR
The increase of the total clearance of VPA caused by MEPM appears to be a consequence of increased renal clearance ofVPA-G, as well as suppression of Vpa-G hydrolysis in the liver.
Panipenum, a carbapenem antibiotic, increases the level of hepatic UDP-glucuronic acid in rats.
TLDR
In vivo treatment with PAPM significantly increased the hepatic UDPGA level by about 1.7-fold and is likely to be one of the causal factors for enhancing VPA glucuronidation in vivo.
Acute Seizures Due to a Probable Interaction between Valproic Acid and Meropenem
TLDR
This case report provides strong evidence for an interaction between valproic acid and meropenem and Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valProic acid serum concentrations.
Epileptic seizures caused by low valproic acid levels from an interaction with meropenem
TLDR
The acute lowering of serum valproate produced by meropenem probably precludes their concomitant use, and may promote the development of epileptic seizures in previously controlled epileptic patients.
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