Objective To investigate the relationship between serum 10-hydroxycarbazepine (MHD, the main active metabolite of oxcarbazepine) concentration and oxcarbazepine efficacy and safety, and to optimize rational use of oxcarbazepine. Methods A total of 553 patients were enrolled in a self-controlled and open-label trial to assess the efficacy and safety of oxcarbazepine as monotherapy. The steady state serum MHD trough concentrations after dose were determined by SPE-HPLC. The relationship between MHD level and efficacy were evaluated by logistic regression model and receiver operating characteristic (ROC) curve. Results A total of 498 patients (90.1%) were effective and 404 patients (73.1%) were seizure free after oxcarbazepine monotherapy in this study. The clinical therapeutic range of steady state serum MHD trough concentrations observed in this study was 5 - 20 mg ? L-1 , and the corresponding 95% distribution interval of oxcarbazepine daily dose was 9. 0 -34.5 mg?kg-1?d-1 . Logistic regression results indicated a positive correlation of antiepileptic efficacy with serum MHD trough concentration within 0.9-30.0 mg?L-1 . The ROC area (95% confidence interval) of MHD trough concentration as the predictor for efficacy was 0.964 (0.938- 0.990), which showed accurate predictions. Most of patients whould have good antiepileptic efficacy while the steady-state serum MHD trough concentration remains above 8 mg?L-1 . Adverse effects were observed in 104 patients (18.8%) during oxcarbazepine dose escalation phase, and 23 patients (4.2%) during maintenance phase. There were no severe adverse effects associated with oxcarbazepine in this study. Patients with serum MHD concentrations >20 mg?L-1 were at greater risk of developing adverse effects. Conclusion Oxcarbazepine therapeutic efficacy and safety are associated with MHD trough level closely, so it is necessary to monitor MHD concentration.

OBJECTIVE: To investigate the value of population pharmacokinetics (PPK) in individualized rescue for an acute lymphoblastic leukemia (ALL) child with severe methotrexate (MTX) excretion delay, and to provide reference for clinical pharmaceutical care. METHODS: Clinical pharmacists participated in clinical rescue for an ALL child with severe MTX excretion delay. The child suffered from severe MTX excretion delay after high dose MTX (HD-MTX) chemotherapy. Clinical pharmacists used PPK model and Bayesian feedback method to predict plasma concentration of MTX. According to measured results and predicted results, rescue dose of calcium folinate (CF) was adjusted to 160 mg/time on the 6th, 7th day after admission for intravenous dripping 1 h, based on initial rescue dose (15 mg/m2, ivgtt, q6 h) of CF; on the 8 th day, CF rescue dose was adjusted to 42 mg/time; on the 9th, 10th day, CF rescue dose was adjusted to 21 mg/time; on the 11th-16th day, CF recue dose was adjusted to 10. 5 mg/ time; 4 times a day. Considering the mild impairment of renal function, clinical pharmacists proposed to discontinue omeprazole and use Cimetidine injection 0. 2 g, ivgtt, qd, for protecting stomach, and decrease the dose of Cefazidime for injection to 0. 4 g, ivgtt, tid; strengthen hydration, alkalization and oral mucosa care. RESULTS: Physicians adopted to the suggestions of clinical pharmacists. The difference between predicted value of plasma concentration of MTX and measured value was less than ± 0. 32 μmol/L. The predictive results showed favorable accuracy. After the adjustment of CF rescue plan under the guidance of PPK model, plasma concentration of MTX decreased to 0. 13 μmol/L. The child completed chemotherapy successfully and discharged from the hospital on the 18th day after admission. CONCLUSIONS: PPK theory can provide reference for clinical rescue in ALL patients with severe MTX excretion delay, and can be used as one of breakthrough points for clinical pharmacists to carry out pharmaceutical care. When the patient suffered from severe MTX excretion delay, clinical pharmacists should fully grasp the influential factors of MTX excretion, and consider the physiological and pathological conditions of the patients, drug combination and plasma concentration, so as to ensure the timely and effective rescue.