| Objective 1.To observe the influence of the combination of carbamazepine(CBZ)and valproate magnesium (VPM) on the threshold for localized seizure in direct cortical stimulation (TLS) model rats and the serum drug concentration.2.nalysis the inter-relationship of the combination of carbamazepine (CBZ) and valproate magnesium (VPM) on the serum drug concentration of some clinical patients.Methods1.The seizure threshold of dynamic change trend and blood drug concentration of rats were observed. The convulsive threshold model was established by direct cortical stimulation and ugular vein catheterization model was found. When the model was stabilized,Forty stable model rats were randomly divided into four groups. N=10.The rats received intragastric administration of CBZ40mg/kg+VPA90mg/kg (high dose group), CBZ20mg/kg+VPA68mg/kg(medium dose group),CBZ10mg/kg+VPA45mg/kg(low dose group) or normal saline (control group), respectively. Three groups of drugs were milling-in and added partes aequales normal saline, collocated with concentrations of 10% of the aqueous solution. Then intragastric administration each one time sooner or later (8:00 Am and 20:00 Pm).after ten times of administration,The convulsive threshold was detected after thirty minutes before the last administration and administration behind thirty minutes, one hours, two hours, four hours, eight hours and twelve hours (seven time points). And taking blood after the last administration four hour. The serum drug concentration peak concentration) was detected after centrifugation with fluorescence polarization immunoassay(FPIA).2.The serum drug concentration curve of CBZ and VPA in patients with refractory epilepsy was analyzed.Selected 32 patients with refractory epilepsy were divided into two groups, first The patients take carbamazepine and valproate magnesium and detect the serum drug concentration with fluorescence polarization immunoassay(FPIA) after one week, Then adding valproate magnesium and carbamazepine respectively.and detecting ampho-concentration after one week,Results 1.Compare with the effect of electrical stimulation cortex convulsion when the combination of arbamazepine (CBZ) and valproate magnesium (VPM) the convulsive threshold in treatment group which after administration at various time points was higher than those in control group, The difference was statistically significant (P<0.05),At 30 min before the last administration, the convulsive threshold in high dose group was higher than those in low dose and medium dose groups, The difference was statistically significant (P<0.05), but there was no significant difference among drug groups at each time point. The difference was no statistically significant(P>0.05)2.Compare with the time-effect relationship of the combination of carbamazepine (CBZ) and valproate magnesium (VPM) After administration for 30 min, all three different doses of drugs worked, and the threshold peaked after administration for 4 h. The anti-convulsion effect of high, medium and low dose drugs maintained 12 h, and the anti-convulsant effect gradually reached the peak, then decreased gradually, Little fluctuation was seen during the period. The convulsant threshold which to reach the same with the low dose group3.Comparison of serum drug concentration of the combination of carbamazepine (CBZ) and valproate magnesium (VPM) in rats. The peak concentration in high dose group was higher than those in medium dose groups, The difference was statistically significant (P<0.05), The peak concentration in medium dose groups was higher than those in low dose groups, The difference was statistically significant (P<0.05), Plasma drug concentration curve of rats showed that the higher the dose was, the higher the peak concentration was. In low dose group,the blood concentration was still in the effective blood drug concentration range.4.the influence of the combination of carbamazepine (CBZ) and valproate magnesium (VPM)on the patients' serum drug concentration. In epilepsy patients, the addition of CBZ or VPA did not influence the plasma concentration of original drugs. The difference was no statistically significant(P>0.05)Conclusion1.The effect of the combination of carbamazepine (CBZ) and valproate acid (VPA) has no significant difference on the threshold for localized seizure in direct cortical stimulation (TLS) model rats, and their serum drug concentration increase with the drug dose.2.1n epilepsy patients, the combination of CBZ or VPA has no influence on the plasma concentration.
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