Uematsu T, Hirayama H, Umemura K, Kosuge K, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Int J Clin Pharmacol Ther. 1994 Jan;32(1):33-7.
A Bayesian approach, in which the estimates of the population pharmacokinetic parameters of lidocaine reported by Vozeh et al. [1984 a and b] and one measurement of serum lidocaine concentration as feedback information were utilized, was prospectively evaluated in 20 Japanese patients. The concentration of lidocaine in serum sampled from each patient at 1.5 to 3 hours after the commencement of i.v. lidocaine therapy was measured and the most likely pharmacokinetic parameters of that patient were predicted by the Bayesian program for microcomputer. Having the predicted parameters, we got the concentrations of lidocaine at 12 and 24 hours (C12 and C24) after starting the therapy within the recommended therapeutic range (2-5 micrograms/ml) by adjusting the individual dosage. As a result, the values of C12 and C24 remained within the therapeutic range in all patients and in all except one, respectively. The mean % prediction error (measured minus predicted concentration standardized by measured one) and its 95% confidence interval were 1.8% and -11.4 to 14.7% for C12, and -2.3% and -11.9 to 7.4% for C24, showing that the prediction of both C12 and C24 was not biased. The correlation coefficients between the measured and predicted concentrations were 0.574 for C12 and 0.721 for C24 (p < 0.01). From these findings, the present Bayesian method implemented with the estimates of pharmacokinetic parameters in a Swiss patient population is useful for sufficiently accurate and precise assessment of individual dosage requirement within a few hours after starting lidocaine therapy.
采用贝叶斯方法,利用沃泽等人[1984年a和b]报告的利多卡因群体药代动力学参数估计值以及一次血清利多卡因浓度测量值作为反馈信息,对20名日本患者进行了前瞻性评估。在静脉注射利多卡因治疗开始后1.5至3小时采集每位患者的血清利多卡因浓度,并通过贝叶斯微机程序预测该患者最可能的药代动力学参数。根据预测参数,通过调整个体剂量,我们在推荐治疗范围内(2 - 5微克/毫升)得出了治疗开始后12小时和24小时(C12和C24)的利多卡因浓度。结果,所有患者的C12值以及除一名患者外所有患者的C24值均保持在治疗范围内。C12的平均预测误差百分比(测量值减去预测浓度,以测量值标准化)及其95%置信区间分别为1.8%和 - 11.4%至14.7%,C24为 - 2.3%和 - 11.9%至7.4%,表明C12和C24的预测均无偏差。测量浓度与预测浓度之间的相关系数,C12为0.574,C24为0.721(p < 0.01)。基于这些发现,采用瑞士患者群体药代动力学参数估计值实施的当前贝叶斯方法,对于在利多卡因治疗开始后数小时内充分准确且精确地评估个体剂量需求是有用的。