A Pharmaceutical Intervention:controlling The Epilepsy Seizure Of Postoperative Brain Injury Based On The Population Pharmacokinetics Of Valproic Acid

Objective:According to the population pharmacokinetics(PPK) model of epilepsy patients by using the nonlinear mixed effects model(NONMEM), this study conducted a pharmaceutical intervention to patients who used the valproic acid(VPA) for preventing the epilepsy seizure of brain injury, and investigate the effect of pharmaceutical care on the incidence of a postoperative epilepsy seizure and on the control of the epilepsy seizure.Methods:1.Retrospective analysis of the serum drug concentration monitoring on VPA,carbamazepine(CBZ) and phenytoin sodium(PHT):The monitoring results and detailed information of VPA,CBZ and PHT serum concentration was collected from April 2012 to April 2015 in a comprehensive three level hospital. The relationship between dose, age, sex, combined use of drugs etc. and the steady-state serum concentration of VPA, CBZ and PHT,and the relationship between serum drug concentration and clinical efficacy were analyzed by the statistical method.2.Study on the population pharmacokinetics of VPA:Population pharmacokinetics model of VPA were respectively established to the children group(age:0-14) and the adult group(age:15-99) by using NONMEM base on the serum concentration of VPA from 2012.04 to 2015.04 in a comprehensive three level hospital. The effect of patients’ general biological characteristics on the VPA pharmacokinetics parameters was quantitatively investigated. Using the Bootstrap method verified the PPK model.3.Pharmaceutical intervention to patients of postoperative brain injury who usedVPA :Patients using VPA for preventing the epilepsy seizure of postoperative brain injury were randomly divided into the intervention group and the control group, who were treated from 2012.6 to 2015.12 in a comprehensive three level hospital. Patients in the intervention group received a series of pharmaceutical care from clinical pharmacists,including the formulation of the initial dose and the dose adjustment based on the PPK model of VPA, the medication and health education, the prevalence of epilepsy-related knowledge, the importance of regular medication, the diet note, the emotion management and the importance of the epilepsy’ risk and prevention, and the discharge education etc.,while patients in the control only recorded the related index and followed up for 6months, did not received pharmaceutical care from clinical pharmacists. Evaluated the practical usefulness of PPK model and the role of clinical pharmaceutical care on the clinical setting by indexs including the incidence and the collect rate of epilepsy after the surgery, the awareness of knowledge about epilepsy, the compliance of VPA(did not miss doses, add and subtract drugs by themselves, taked medicine on time, periodically reviewed the serum drug concentration and maintained good living habits), the incidence of adverse drug reaction, the target rate of VPA serum drug concentration,etc.Results:1.Retrospective analysis of the serum drug concentration monitoring on VPA,CBZ and PHT:A total of 542 steady state serum concentrations were collected in patients with epileptic, including 371 cases of VPA, 132 cases of CBZ, 39 cases of PHT. The effective serum drug concentrations proportion of VAP, CBZ and PHT were respectively 50.2%、70.5% and 15.4%.2. Study on the population pharmacokinetics of VPA:Children group(age:0-14): CL= 0.0784+0.00238×WT+0.189×TDD; Adult group(age:15-99): CL=0.442×(WT/60)0.374×TDD0.306×1.24 CBZ, WT means weight(kg); TDD means daily dose of VPA(g). CBZ was 1 when treated with carbamazepine, otherwiseCBZ was 0. The final model of both children and adults groups had been proved to have the high stability and reliability by the bootstrap method.3.Pharmaceutical intervention to patients of postoperative brain injury who used VPA :The incidence of epilepsy, the awareness of knowledge about epilepsy, the incidence of adverse drug reaction, the target rate of VPA serum drug concentration in the intervention group were significantly better than the control group(P<0.05). In terms of the compliance, the patients in the intervention group were significantly improved in taking medicine on time, not missing doses and periodically reviewing the serum drug concentration(P<0.05), while there was no significant difference between the two groups in not adding, subtracting drugs by themselves and maintaining good living habits(P>0.05).Conclusion:1.The established PPK model of VPA by the NONMEM method is stable and effective, has the good ability of prediction, and could provide the reference for the clinical individual treatment.2.Pharmaceutical care provided by clinical pharmacists has a positive role on preventing the incidence of epilepsy after the surgery and controlling the epilepsy seizure,it also can significantly improve the patient’s medication compliance and the awareness of the disease and drug-related knowledge.