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Sodium valproate (VPA) is a first-line prescription drug widely used in the treatment of epilepsy. However, in clinical applications, it has been found that there is a large individual variation in the blood concentration of VPA. In particular, excessively high blood drug concentrations can lead to various side effects, especially hepatotoxicity. Blood drug concentration monitoring can reduce the toxic and side effects of VPA to a certain extent and improve its effectiveness, but it is too cumbersome. A large number of studies have shown that the efficacy and toxic side effects of VPA are closely related to its in vivo metabolism process. The in vivo metabolism of VPA is affected by many factors, and the genetic polymorphism of drug-metabolizing enzymes is an important factor leading to differences in blood drug concentrations and affecting the dosage of VPA. The three products generated by the biotransformation of VPA by CYP450 enzymes are all related to hepatotoxicity. The formation of 4-ene-VPA is largely catalyzed by CYP2C9 and CYP2A6. Mutations in the CYP2A6 gene may be related to VPA hepatotoxicity, but there is a lack of further direct evidence. 50% of VPA in the body is acidified and metabolized into inactive products by uridine diphosphate glucuronosyltransferase (UGT) through phase II conjugation reactions. However, there is evidence that the genetic polymorphism of UGT can significantly affect the blood drug concentration of metformin. Based on the above research, we selected CYP2A6, UGT1A6, etc. as candidate genes, and studied the impact of genetic polymorphisms on the individual differences of sodium valproate through association analysis, with the hope of establishing a genetic model for optimal dosage and providing new strategies for the individualized use of VPA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium valproate | Experimental | According to the dosage forms of sodium valproate, they are divided into the sodium valproate tablet group, the sodium valproate oral solution group and the sodium valproate sustained-release tablet group. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sodium valproate | Drug | All three groups are administered twice a day via oral administration. Patients are given different doses based on their body weight and the therapeutic effect in controlling epilepsy. |
| Measure | Description | Time Frame |
|---|---|---|
| The blood concentration of valproic acid | The effective blood concentration of valproic acid should be maintained at 50 - 100 ug/mL. | Collect data on the first patient and follow up for a period of three years. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jiecan Zhou, Prof. | Contact | +86-734-8279018 | zhoujiecan@fsyy.usc.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of University of South China | Recruiting | Hengyang | Hunan | 421001 | China |
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| ID | Term |
|---|---|
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D014635 | Valproic Acid |
| ID | Term |
|---|---|
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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| D009930 |
| Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |