Richens A
Department of Clinical Pharmacology, St. Bartholomew's Hospital, London, England.
Epilepsia. 1975 Nov;16(4):627-46. doi: 10.1111/j.1528-1157.1975.tb04745.x.
Phenytoin is metabolized to its parahydroxylated derivative by hepatic microsomal enzymes. This hydroxylation is a saturable process, that is, the rate of metabolism fails to increase in proportion to the serum concentration. This leads to a nonlinear relationship between the maintenance dose of the drug and the resulting steady-state serum level. As the therapeutic range of serum levels is reached, the increase in level produced by a given increment in dose becomes progressively greater. An increment of only 50-100 mg will carry the serum level from the lower to the upper limit of the therapeutic range in most patients. Thus, problems in bioavailability, noncompliance, and drug interactions are an important practical problem with this drug. Monitoring serum phenytoin levels during chronic therapy is an invaluable therapeutic aid, enabling dosage adjustments to be made in order to achieve a level within the therapeutic range. A nomogram is presented in this paper in order to assist the physician in making dosage increments.
苯妥英通过肝脏微粒体酶代谢为其对羟基化衍生物。这种羟基化是一个可饱和的过程，也就是说，代谢速率不会与血清浓度成比例增加。这导致药物维持剂量与由此产生的稳态血清水平之间呈非线性关系。当达到血清水平的治疗范围时，给定剂量增量所产生的水平升高会逐渐变大。在大多数患者中，仅增加50 - 100毫克就能使血清水平从治疗范围的下限升至上限。因此，生物利用度、不依从性和药物相互作用方面的问题是该药物一个重要的实际问题。在长期治疗期间监测血清苯妥英水平是一种非常有价值的治疗辅助手段，能够进行剂量调整以达到治疗范围内的水平。本文给出了一个列线图，以帮助医生进行剂量增加。
