Related Experiment Video
Updated: Sep 18, 2025
09:37
Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine
Published on: August 24, 2018
10.6K
Risk Factors and Multiple Interaction Effects for Hyperammonemia in Patients Receiving Valproic Acid
Chien-Chou Su1, Tsai-Kuei Huang2, Ching-Sen Shih3
1Clinical Innovation and Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Fundamental & Clinical Pharmacology
|June 22, 2025
Summary
Valproic acid (VPA) use increases hyperammonemia (HA) risk. Younger patients, those with epilepsy, or on polypharmacy face higher risks, especially with elevated VPA levels.
Area of Science:
- Pharmacology
- Clinical Toxicology
- Data Science
Background:
- Valproic acid (VPA) is linked to hyperammonemia (HA) risk.
- Interactions of HA risk factors in VPA-treated patients are not fully understood.
Purpose of the Study:
- Identify and assess interactions of HA risk factors in VPA-treated patients.
- Improve clinical risk stratification for VPA therapy.
Main Methods:
- Retrospective cohort study (2019-2021).
- SHapley Additive exPlanations (SHAP) for model interpretation and interaction analysis.
- Analysis of risk factor interactions affecting HA.
Main Results:
- Top 15 HA predictors identified: age, VPA concentration, VPA dose, epilepsy, VPA duration, levetiracetam, hypertension, mental disorders, medication count.
- Significant interactions: age with VPA concentration, epilepsy, and treatment duration.
- Younger patients, elevated VPA, epilepsy, or polypharmacy increase HA risk.
Conclusions:
- Key factors influencing HA in VPA patients identified, especially in younger individuals, those with epilepsy, or on polypharmacy.
- Findings require further validation due to retrospective, single-center design.
Related Concept Videos
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
461
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...
461
01:14Antiepileptic Drugs: Glutamate Antagonists
527
Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
527
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
312
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
312
01:23Factors Affecting Protein-Drug Binding: Drug Interactions
291
Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
291
01:16Hepatic Drug Excretion: Influencing Factors
242
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
242
01:29Factors Affecting Protein-Drug Binding: Patient-Related Factors
123
Protein-drug binding, a pivotal aspect of pharmacokinetics, is subject to considerable variability influenced by an array of patient-related factors. The intricate interplay of age, individual differences, and pathological conditions significantly impact the binding dynamics and subsequent pharmacological effects.
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
123