Browne T R, Evans J E, Szabo G K, Evans B A, Greenblatt D J, Schumacher G E
J Clin Pharmacol. 1985 Jan-Feb;25(1):43-50. doi: 10.1002/j.1552-4604.1985.tb02799.x.
Six patients were given tracer doses of 13C15N2-phenytoin (PHT) before and four and 12 weeks after beginning monotherapy. The following significant (P less than .05) changes occurred during monotherapy: (1) Apparent (from tracer doses) PHT total clearance by linear method decreased; (2) apparent PHT elimination half-life increased; (3) apparent mean PHT serum concentration per unit dose increased; (4) apparent rate of excretion of p-hydroxyphenyl-phenylhydantoin (p-HPPH) decreased; (5) apparent rate of excretion of PHT dihydrodiol increased; and (6) apparent PHT total clearance and elimination half-life and apparent p-HPPH rate of excretion were dose dependent. Phenytoin apparent pharmacokinetic and biotransformation values undergo a typical series of changes after beginning monotherapy at typical dosing rates, because PHT's dose-dependent pharmacokinetics result in differing apparent values as the serum concentration rises to steady state. Stable isotope methods are particularly suitable for investigating such phenomena.
6名患者在开始单一疗法前、开始单一疗法4周和12周后接受了示踪剂量的13C15N2 - 苯妥英（PHT）。在单一疗法期间发生了以下显著（P < 0.05）变化：（1）通过线性方法测得的（来自示踪剂量）PHT总清除率降低；（2）PHT消除半衰期延长；（3）每单位剂量的PHT血清平均浓度升高；（4）对羟基苯基苯妥英（p - HPPH）的排泄率降低；（5）PHT二氢二醇的排泄率升高；（6）PHT总清除率、消除半衰期以及p - HPPH排泄率与剂量相关。苯妥英的表观药代动力学和生物转化值在以典型给药速率开始单一疗法后会经历一系列典型变化，因为PHT的剂量依赖性药代动力学导致随着血清浓度升至稳态时表观值有所不同。稳定同位素方法特别适合研究此类现象。
