Predictive Performance Of Oral Phenytoin For The Prophylaxis Of Early Seizure After Craniocerebral Injury And Phenytoin Prophylactic Therapy Against Early After Craniocerebral Injury:a Meta Analysis

Part one Phenytoin Prophylactic on Early Epilepsy after Craniocerebral Injury.---A Meta-analysisObjective: To evaluate the prophylactic efficacy of Phenytion against epilepsy after craniocerebral injury by Meta-analysis.Methods:Relevant RCTs were identified by searching electronic databases including Medline,Pubmed,Embase,Cochrane Library,CNKI,CBM and WANFANG.Eligible articles were included to extract data.Relative risk(RR)was used to analyze the ratios of early seizures.Inter-study heterogeneity was evaluated by using Chi-square test-based Q test.I2 was used to quantify the effect of heterogeneity.A fixed-effect model was employed to calculate the pooled effects if P >0.1 or I <50% test P >0.1 or I < 50%;otherwise,a randomized-effect model was used.Result: A total of 1487 unduplicated papers were identified.And 1378 papers of them were excluded by reading the abstracts and titles.Another 101 papers were excluded after reading their complete text.Eventually 8papers on random control trials(RCTs)were included.These 8 literatures included1657 patients,861 patients in phenytoin group and 796 patients in placebo or no treatment control group.There was no significant heterogeneity between literatures.Fixed-effect model was used for the analysis.Results showed phenytoin group had less early seizures in the craniocerebral injury patients(RR=0.38,95%CI:0.26,0.56,P < 0.00001),and craniocerebral trauma patients(RR=0.33,95%CI : 0.19,0.59,P=0.0002)and the craniocerebral upper –curtain surgery patients(RR=0.43,95%CI:0.25,0.71,P=0.001)than control group.Conclusion: Phenytoin can effectively prevent early epilepsy after craniocerebral injury.Part two Predictive Performance of Oral Phenytoin for the Prophylaxis of Early Seizure after Craniocerebral injuryBackground and Objective: The objectives of this study were to evaluate the predictive performance of having established population pharmacokinetic(PPK)models of oral phenytoin for the prophylaxis of early seizure after craniocerebral injury on the basis of NONMEM program and to ensure which of the models is most fit for Chinese population after craniocerebral injury.Method: Bayesian method was used to evaluate the predictive performance of the three models established based on different kinds of genetypes,body weight,temperature,peak concentrations and trough concentrations.Results: Four hundred and fourty-one blood concentrations from 151 Chinese adult patients with intracranial tumor during the first week of post-craniotomy were collected to serve as the test data set.Three models had similar prediction in body weight subpopulations.Model 3 and model 2 had better prediction for the abnormal temperature subpopulations.Observations in the peak concentration group were predicted better by three models.Model 1 and model 3 gave better predictons for the patients with extensive metabolizers subpopulations.Three models had similar predictability between the poor metabolizers and intermediate metabolizers subpopulations.Conclusions: Based on 3 different external validation data,the performance of three evaluated models varied.The distribution of covariates should be given more consideration when a model was to choose to predict blood concentrations.Model 3 is appropriate for Bayesian dose prediction for phenytoin concentrations in our population.