해마경화증을 동반하지 않은 신피질성 측두엽간질의 수술적 치료 효과와 예후 인자에 대한 연구

Thesis(masters) --서울대학교 대학원 :의학과(뇌신경과학 전공),2010.2.Maste

Factors Influencing Topiramate Pharmacokinetics in Adult Patients with Epilepsy: A Population Pharmacokinetic Analysis

학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2015. 2. 이상건.Background: Topiramate is widely used as an antiepileptic drug (AED) in the treatment of epilepsy. The pharmacokinetics (PK) of topiramate are known to be influenced by various factors such as age, renal function, and concomitant medication. However, these factors have not been thoroughly quantified and remain controversial. The objective of the present study was to identify the factors influencing topiramate PK in a large population of adult patients with epilepsy using population PK analysis. Materials and Methods: Clinical data and blood samples were collected from 553 adult patients with epilepsy treated using topiramate with or without concomitant AEDs. Plasma concentrations of topiramate in a steady state were determined by liquid chromatography-tandem mass spectrometry. Nonlinear mixed effects modeling software (NONMEM, version 7.2) was used to fit the plasma concentration to a one-compartment PK model. Demographic and clinical variables tested as potential covariates were age, sex, body weight, height, serum creatinine, creatinine clearance (CLcr), total bilirubin, prothrombin time, albumin, aspartate transaminase (AST), alanine transaminase (ALT), daily dose (DOSE), and concomitant medications (phenytoin [PHT], clobazam, carbamazepine [CBZ], valproic acid, lamotrigine, levetiracetam, oxcarbazepine [OXC], pregabalin, clonazepam, and phenobarbital [PB]). In addition, the efficacy and adverse events of topiramate were analyzed according to the level of daily dose per body weight and plasma concentration. Results: The final PK model was CL/F (L/h) = (1.17 + 1.36×PHT + 1.02×CBZ + 0.621×OXC + 0.488×PB) × (CLcr/90)0.289 × (DOSE/100)0.0894 (1 in patients co−medicated with each drug, 0 in otherwise) and V/F (L) = 108 × (WT/62). For a typical patient with CLcr of 90 mL/min and DOSE of 100 mg, the CL/F was expected to be 1.17 L/h. Co−medication with PHT, CBZ, OXC, and PB increased the CL/F to 2.53 (1.17+1.36) L/h, 2.19 (1.17 + 1.02) L/h, 1.791 (1.17+0.621) L/h, and 1.658 (1.17+0.488) L/h, respectively, which was 116%, 87%, 53%, and 42% higher, respectively, than in patients without co-medication. Two hundred sixty-four patients (48%) were seizure free, 236 (43%) had at least 50% seizure reduction, and 52 (9%) had less than 50% seizure reduction. One hundred thirty-eight patients (25%) reported adverse events, including memory impairment, dizziness, anomia, weight loss, paresthesia, and appetite loss. The efficacy and adverse events of topiramate did not show any clinically relevant relationship with the daily dose per body weight or plasma concentration. Conclusion: The apparent clearance of topiramate increased with co-medication of PHT, CBZ, OXC, and PB. This population PK model can be applied for optimizing topiramate dosage regimens in actual clinical practice, especially for the patients on polytherapy with PHT, CBZ, OXC, and PB. Individualization of therapeutic dose and plasma concentration is needed for epilepsy patients treated with topiramate.Abstract ———————————————————— 1 Contents———————————————————— 3 List of tables and figures————————————— 4 Introduction——————————————————— 5 Materials and methods—————————————— 6 Results————————————————————— 9 Discussion ——————————————————— 10 References ——————————————————— 14 Tables and figure legends———————————— 17 국문 초록 ——————————————————— 26Docto

Emergency Superficial Temporal Middle Cerebral Artery Bypass Surgery for Acute Symptomatic Middle Cerebral Artery Occlusion With Hemodynamic Disturbance

The role of surgical revascularization for patients with ischemic stroke remains controversial. During acute phase of large artery occlusive ischemic stroke, extracranial?intracranial (EC-IC) bypass, such as superficial temporal-middle cerebral aretery (STA-MCA) bypass sugery, has been rarely performed. We report a case of successful emergency STA-MCA bypass surgery to stop the neurologic deterioration and improve the hemodynamic compromise in a patient with acute symptomatic MCA occlusion associated with hypoperfusion.N