Population pharmacokinetics of oxcarbazepine in Chinese epilepsy patients / 药学学报

Oxcarbazepine (OXC) is a common antiepileptic drugs. In this study, one hundred and eighty four epilepsy patients with 196 observations of oxcarbazepine's active metabolite, 10,11-dihydro-10-monohydroxy carbazepine (MHD) were collected prospectively from routine clinical monitoring. Nonlinear mixed effect modeling was employed to develop a population pharmacokinetic model of oxcarbazepine in Chinese patients with epilepsy to investigate the impact of gender, age, weight, co-medications and genetic polymorphisms of UGT2B7 c.802T>C, ABCC2 c.1249G>A, ABCC 23972C>T on pharmacokinetic characteristics of OXC. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 1.84 L·h−1 and 275 L, respectively. Gender and UGT2B7 c.802T>C affected the clearance rate of MHD significantly. The established model was:CL/F=1.84×0.848UGT2B7×1.17GENDER. Where the genotype of UGT2B7 c.802T>C was CC, UGT2B7=0, otherwise UGT2B7=1. When the patient was male, GENDER=1, otherwise GENDER=0. The final model was evaluated by normalized predictive distribution error (NPDE) and bootstrap method. The model was stable and reliable, which offers a powerful approach for rational use of OXC in epilepsy patients.

Tenidap is neuroprotective in a pilocarpine rat model of temporal lobe epilepsy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE).</p><p><b>METHODS</b>Tenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus (SE) in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures (SRSs) were recorded by video monitoring (for 7 hours per day for 14 days). The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death.</p><p><b>RESULTS</b>There were 46.88 ± 10.70 survival neurons in tenidap-SE group, while there were 27.60 ± 5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75 ± 8.78 survival neurons in tenidap-SE group, while there were 33.40 ± 8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area (P < 0.05) and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area.</p><p><b>CONCLUSION</b>Tenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.</p>

Alterations in KCNJ4 gene expression in human temporal lobe epilepsy / 中华神经科杂志

Objective To evaluate the possible molecular pathogenesis of intractable temporal lobe epilepsy. The potassium ion channel gene KCNJ4 encodes one of the subfamilies of Kir channels, Kir2.3 subunit, which may play an important role in modulating neuronal excitation. Interference in the function or expression of this gene would cause disturbance of ionic concentrations, thus leading to seizure activity. Methods Reverse transcription polymerase chain reaction (RT-PCR) and Western-blot analysis were used to measure the expression alterations of KCNJ4 mRNA as well as its protein product Kir2.3 channel in temporal cortex samples from patients who had undergone temporal lobectomy for intractable epilepsy (n=12). Tissue from 10 subjects who did not have epilepsy served as controls. Results The expression of KCNJ4 mRNA (0.438?0.178) and its protein Kir2.3 (M 50=0.063) were significantly decreased in epileptic brain compared with the controls (P