PURPOSE: Status epilepticus (SE) is a pathologic state where pharmacokinetic alterations can be more pronounced and more rapid than during the other epileptic states. The consequences of such changes can exert negative influences on the timely adequate treatments for stopping uncontrolled seizures during SE. Topiramte (TPM) is one of new antiepileptic drugs with high efficacy in epilepsy, which can also be effectively used in SE. The aim of this study was to evaluate the pharmacokinetic changes during the SE by an analysis of the therapeutic drug monitoring (TDM) of TPM in patients with SE.METHODS: We retrospectively analyzed 49 serum measurements of TPM from 22 subjects with SE. The serum concentrations of TPM were measured by HPLC-tandem mass spectrometry. TDM data were categorized into malignant status epilepticus (MSE), refractory status epilepticus (RSE), and non-status epilepticus (NSE) groups. We compared concentration-to-dose ratio (CDR) among those groups.RESULTS: Among 49 cases, 11 were in MSE, 19 in RSE, and 19 in NSE. The daily dose of TPM was higher in MSE (median, interquartile range: 600, 600-800 mg) than in RSE (300, 250-600 mg) and NSE (200, 150-400 mg). The daily dose adjusted for body weight was also higher in MSE (12.2, 10.4-13.9 mg/kg) than in RSE (4.5, 3.8-12.2 mg/kg) and NSE (4.1, 2.3-7.1 mg/kg) (p<0.01). Serum concentrations of TPM were less in MSE (5.8, 4.2-7.3 mg/L) and RSE (4.9, 2.9-6.0 mg/L) than in NSE (5.5, 3.3-9.0 mg/L), which were not significantly different among the groups (p>0.1). However, the concentration-to-dose ratio (CDR) was significantly lower in MSE (0.41, 0.35-0.59 kg/L) and RSE (0.85, 0.39-1.23 kg/L) than in NSE (1.72, 0.96-2.24 kg/L) (post hoc analysis, p<0.005, 0.05).CONCLUSIONS: The serum concentrations of TPM can be influenced by SE, particularly in MSE. The higher range of dose of TPM could be needed for an adequate treatment of SE.
Anticonvulsants ; Body Weight ; Drug Monitoring ; Epilepsy ; Fructose ; Humans ; Mass Spectrometry ; Retrospective Studies ; Seizures ; Status Epilepticus

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy.
Adult ; Bilirubin/*blood ; Disease Progression ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications ; Humans ; Hypertension/complications ; Incidence ; Kidney Failure, Chronic/*blood/complications ; Male ; Middle Aged ; Risk ; Risk Factors ; Treatment Outcome