Browne T R, Evans J E, Szabo G K, Evans B A, Greenblatt D J
J Clin Pharmacol. 1985 Jan-Feb;25(1):51-8. doi: 10.1002/j.1552-4604.1985.tb02800.x.
Six healthy adults receiving no other medications were given tracer doses of 90 mg of stable isotope-labeled phenobarbital (PB) intravenously before, and four weeks after, and 12 weeks after beginning therapy. Serum samples were collected for 96 hours after each injection, and the concentration of stable isotope-labeled PB in each sample was determined by gas chromatographic mass spectrometry. The volume of distribution, elimination half-life, and total clearance of PB did not differ significantly on any of the three occasions measured. Phenobarbital clearance did not correlate significantly with total PB serum concentration. Clearances determined from single-dose studies before beginning PB therapy accurately predicted steady-state PB serum concentrations. Therefore, it is not necessary to adjust PB dosage for time-dependent or dose-dependent changes in clearance during monotherapy. In addition, clearance or serum concentration determined at one dosing rate directly predicts serum concentration at another dosing rate.
六名未服用其他药物的健康成年人在开始治疗前、治疗四周后和治疗十二周后静脉注射了示踪剂量的90毫克稳定同位素标记的苯巴比妥（PB）。每次注射后收集血清样本96小时，并通过气相色谱 - 质谱法测定每个样本中稳定同位素标记的PB浓度。在三次测量的任何一次中，PB的分布容积、消除半衰期和总清除率均无显著差异。苯巴比妥清除率与血清总PB浓度无显著相关性。在开始PB治疗前从单剂量研究确定的清除率准确预测了PB血清稳态浓度。因此，在单一疗法期间，无需因清除率的时间依赖性或剂量依赖性变化而调整PB剂量。此外，以一种给药速率测定的清除率或血清浓度可直接预测另一种给药速率下的血清浓度。
