Klotz U
J Clin Chem Clin Biochem. 1983 Nov;21(11):649-58.
The response to a given drug dose varies widely among patients. This is mainly due to the intra- and interindividual variation in the patients' pharmacokinetics. Individual pharmacokinetic parameters (bio-availability, elimination half-life, apparent volume of distribution, clearance, plasma protein binding) can be calculated from single or multiple dose studies. One should be aware that the age of the patient, his kidney, liver, heart and thyroid function might have a great influence on the pharmacokinetics of a particular drug. The pharmacokinetic parameters can be also estimated for a population of patients by fitting data from routine plasma level monitoring to computer programs, such as NONMEM. For drugs with a narrow therapeutic index, dosage is often based on the measurement of plasma concentrations, which serve as a therapeutic/diagnostic end point. There are various procedures (e.g. nomograms, test doses) for predicting the dosage regimen necessary to achieve so-called therapeutic concentrations in an individual. The general Bayes approach improves forecast precision by combining prior knowledge (population kinetics) with current evidence (measurements of plasma concentrations). Thus, therapeutic drug monitoring and pharmacokinetics can contribute to a more effective and safe therapy.
患者对给定药物剂量的反应差异很大。这主要是由于患者药代动力学的个体内和个体间差异。个体药代动力学参数(生物利用度、消除半衰期、表观分布容积、清除率、血浆蛋白结合率)可通过单剂量或多剂量研究计算得出。应注意,患者的年龄、肾脏、肝脏、心脏和甲状腺功能可能对特定药物的药代动力学有很大影响。通过将常规血浆水平监测数据拟合到计算机程序(如NONMEM),也可以为一群患者估算药代动力学参数。对于治疗指数窄的药物,剂量通常基于血浆浓度的测量,血浆浓度作为治疗/诊断终点。有各种程序(如列线图、试验剂量)用于预测个体达到所谓治疗浓度所需的给药方案。通用贝叶斯方法通过将先验知识(群体动力学)与当前证据(血浆浓度测量)相结合来提高预测精度。因此,治疗药物监测和药代动力学有助于实现更有效和安全的治疗。