Related Experiment Video
Updated: Jul 9, 2026
12:03
Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
Interaction between valproic acid and carbapenem antibiotics.
Hitomi Mori1, Kazuhiko Takahashi, Takaharu Mizutani
1Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Drug Metabolism Reviews
|December 7, 2007
Summary
Carbapenem antibiotics significantly lower valproic acid (VPA) levels in epilepsy patients. This review explores mechanisms involving intestinal absorption, liver metabolism, and blood distribution that reduce VPA concentration, impacting treatment efficacy.
Area of Science:
- Pharmacology
- Drug Interactions
- Epilepsy Treatment
Background:
- Valproic acid (VPA) is a key antiepileptic drug.
- Carbapenem antibiotics (e.g., meropenem) can reduce serum VPA concentrations.
- This interaction can lead to sub-therapeutic VPA levels, risking treatment failure.
Purpose of the Study:
- To review and elucidate the mechanisms behind the VPA concentration decrease induced by carbapenem antibiotics.
- To summarize case reports and experimental findings on this drug interaction.
Main Methods:
- Review of case reports on VPA-carbapenem interactions.
- Experimental studies in rats investigating VPA absorption, hepatic metabolism, blood distribution, and renal excretion.
- In vitro studies using human liver microsomes.
Main Results:
- Carbapenem antibiotics may reduce VPA absorption by inhibiting intestinal transporters or decreasing bacterial beta-glucuronidase activity.
- Hepatic mechanisms include decreased UDP-glucuronosyltransferase (UGT) cofactor UDPGA, direct UGT activation, or inhibition of hepatic beta-glucuronidase.
- Carbapenems may affect VPA distribution by inhibiting erythrocyte efflux transporters (Mrp4).
Conclusions:
- Multiple mechanisms, including altered intestinal absorption, hepatic metabolism, and blood distribution, contribute to carbapenem-induced VPA level reduction.
- Understanding these mechanisms is crucial for managing epilepsy patients on both VPA and carbapenem therapy.
- Further research may clarify the precise contribution of each mechanism to the observed VPA concentration decrease.
Related Concept Videos
01:27Combined Effects of Drugs: Synergism
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
01:30Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
01:25Pharmacokinetics: Drug–Drug Interactions
Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
01:26Pharmacokinetics: Drug–Food and Drug–Viral Interactions
A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of many...
01:23Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...