Pugh C B, Garnett W R, Poynor W J, Pellock J M
Clin Pharm. 1984 Nov-Dec;3(6):643-9.
Valproic acid serum concentrations predicted by a single-dose prediction model were compared with steady-state serum concentrations measured after the start of therapy in seizure patients. Ten patients receiving valproic acid for the first time or who had not been taking the drug for two or more weeks were entered into the study. The patients' therapies were initiated with the prescribed doses of valproic acid and then maintained on fixed doses and dosing intervals until steady-state trough serum samples were obtained. Initial 5-ml blood samples were collected six to 14 hours after the ingestion of the first dose; a 5-ml steady-state trough sample was drawn in the same manner three to seven days later. Both free and total drug concentrations were determined within 48 hours of sample collection using gas-liquid chromatography. The elimination rate constant was estimated from age-specific population half-life values found in the literature. Six patients (five children, aged four to 16 years) and one adult (aged 87 years) completed the study. There was a statistically significant correlation between predicted and measured steady-state valproic acid serum concentrations for both free and total concentrations. The single-dose prediction model accurately predicted steady-state valproic acid serum concentrations in these seizure patients.
将单剂量预测模型预测的丙戊酸血清浓度与癫痫患者开始治疗后测得的稳态血清浓度进行比较。10例首次接受丙戊酸治疗或已停药两周或更长时间的患者进入该研究。患者的治疗开始时给予规定剂量的丙戊酸，然后维持固定剂量和给药间隔，直至获得稳态谷血清样本。首次给药后6至14小时采集初始5毫升血样；3至7天后以相同方式采集5毫升稳态谷样本。在样本采集后48小时内使用气液色谱法测定游离和总药物浓度。消除速率常数根据文献中特定年龄的群体半衰期值估算。6例患者（5名儿童，年龄4至16岁）和1名成人（87岁）完成了研究。游离和总浓度的预测稳态丙戊酸血清浓度与实测浓度之间存在统计学显著相关性。单剂量预测模型准确预测了这些癫痫患者的稳态丙戊酸血清浓度。
