Browne T R, Greenblatt D J, Harmatz J S, Evans J E, Szabo G K, Evans B A, Schumacher G E
J Clin Pharmacol. 1985 Jan-Feb;25(1):59-63. doi: 10.1002/j.1552-4604.1985.tb02801.x.
Stable isotope labeled tracer doses of phenytoin (PHT) and phenobarbital (PB) were given intravenously before and four and 12 weeks after beginning monotherapy in two groups of six patients. Phenytoin demonstrated nonlinear pharmacokinetics, while PB demonstrated linear pharmacokinetics. Each of the 36 sets of tracer dose serum concentration versus time data points appeared linear during the elimination phase on semilog plots, and each demonstrated a high degree of linearity using semilog regression analysis (r2 = .977-.999, P less than .001, for PHT; r2 = .791-.996, P less than .005, for PB). We conclude tracer doses administered at steady-state serum concentration will exhibit linear serum concentration versus time relationships on semilog plots regardless of whether the steady-state serum concentration is in the linear or the nonlinear portion of a drug's dose versus steady-state serum concentration relationship. The mechanism and implications of this conclusion are discussed.
在两组各六名患者中，在开始单一疗法之前、之后四周和十二周时静脉注射稳定同位素标记的苯妥英（PHT）和苯巴比妥（PB）示踪剂量。苯妥英表现出非线性药代动力学，而PB表现出线性药代动力学。在半对数图上，36组示踪剂量血清浓度与时间数据点中的每一组在消除阶段均呈线性，并且使用半对数回归分析均显示出高度线性（PHT的r2 = 0.977 - 0.999，P < 0.001；PB的r2 = 0.791 - 0.996，P < 0.005）。我们得出结论，无论稳态血清浓度处于药物剂量与稳态血清浓度关系的线性部分还是非线性部分，在稳态血清浓度下给予的示踪剂量在半对数图上均会呈现血清浓度与时间的线性关系。讨论了该结论的机制和意义。
