Pitlick W, Painter M, Pippenger C
Clin Pharmacol Ther. 1978 Mar;23(3):346-50. doi: 10.1002/cpt1978233346.
Phenobarbital pharmacokinetics after intravenous injection were studied in 8 neonates with seizures. Subjects ranged in gestational age from 30 to 40 wk. Plasma concentrations of phenobarbital were measured by enzyme-multiplied immunoassay (EMIT). The volume of distribution (Vd) of phenobarbital was 0.97 +/- .15 L/kg which was independent of the dose administered. Vd and gestational age did not correlate. Phenobarbital clearance calculated from average concentrations in patients maintained on phenobarbital for 1 to 4 wks was consistent, with a decrease in t1/2 from 115 hr after 1 wk to 67 hr after 4 wk of therapy. The elimination of phenobarbital decreased at an exponential rate with a t1/2 of 4.6 days. A pharmacokinetic model with an exponentially increasing elimination rate term was used to describe the data. Average concentrations predicted with the use of the model corresponded adequately with experimental results. The increases in clearance observed are thought to be related to rates of turnover of drug-metabolizing enzymes in the neonate.
对8例癫痫发作的新生儿静脉注射苯巴比妥后的药代动力学进行了研究。研究对象的胎龄为30至40周。采用酶放大免疫测定法（EMIT）测定苯巴比妥的血浆浓度。苯巴比妥的分布容积（Vd）为0.97±0.15L/kg，与给药剂量无关。Vd与胎龄无相关性。根据接受苯巴比妥治疗1至4周患者的平均浓度计算出的苯巴比妥清除率是一致的，治疗1周后t1/2从115小时降至4周后的67小时。苯巴比妥的消除呈指数下降，t1/2为4.6天。使用消除速率项呈指数增加的药代动力学模型来描述数据。使用该模型预测的平均浓度与实验结果充分相符。观察到的清除率增加被认为与新生儿药物代谢酶的周转速率有关。
