Browne T R, Van Langenhove A, Costello C E, Biemann K, Greenblatt D J
Clin Pharmacol Ther. 1981 Apr;29(4):511-5. doi: 10.1038/clpt.1981.71.
Stable isotope labeling (SIL) of a drug results in a higher molecular weight than that of the unlabeled drug. SIL tracer doses can be quantitated separately from unlabeled drug by gas chromatography-mass spectrometry (GC-MS) without exposing the patient to radiation. The higher molecular weight of SIL drug could cause a higher energy of activation for (and slowing of) metabolic reactions ("isotope effect"). To evaluate possible isotope effect, three dogs and three men were infused with a mixture containing equal amounts of SIL (2-13C-1,3-15N2) and unlabeled phenytoin (PHT). Plasma and urine were collected at regular intervals. Concentrations of SIL and unlabeled PHT and HPPH (the major metabolite of PHT) were determined by GC-MS. Within each subject there was no trend for concentrations of SIL PHT or HPPH to be higher or lower than concentrations of their unlabeled analogs (greater than 0.20 to 0.90). There was no difference in the distribution and elimination half-lifes (t 1/2s), volume of distribution, volume of central compartment, or clearance of the two forms of PHT. Thus, no isotope effect was found.
药物的稳定同位素标记（SIL）会使其分子量高于未标记的药物。通过气相色谱 - 质谱联用（GC - MS）可将SIL示踪剂量与未标记药物分开定量，且不会使患者暴露于辐射之下。SIL药物较高的分子量可能会导致代谢反应的活化能升高（以及代谢反应减慢）（“同位素效应”）。为评估可能的同位素效应，对三只狗和三名男性输注了含有等量SIL（2 - 13C - 1,3 - 15N2）和未标记苯妥英（PHT）的混合物。定期采集血浆和尿液。通过GC - MS测定SIL、未标记的PHT和HPPH（PHT的主要代谢产物）的浓度。在每个受试者中，SIL PHT或HPPH的浓度没有高于或低于其未标记类似物浓度的趋势（大于0.20至0.90）。两种形式的PHT在分布和消除半衰期（t 1/2s）、分布容积、中央室容积或清除率方面没有差异。因此，未发现同位素效应。
