Brocks D R, Lee K C, Tam Y K, Weppler C P, Bradley J M
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Ther Drug Monit. 1988;10(1):58-63.
Requirements for regular-release oral theophylline were determined in 34 pediatric patients aged 0.25-14.8 years using orally derived pharmacokinetic data and the first-order absorption equation. Large ranges were found in the half-life (2.3-21.3 h) and calculated apparent volume of distribution (Vd) (0.300-1.54 L/kg). Mean serum theophylline concentration was more closely correlated with actual mean concentration (r = 0.61, p less than 0.0002) when calculated with the individual patients' Vd values than with the standard Vd of 0.5 L/kg (r = 0.31, NS), and predictions obtained with the individuals' Vd values were more precise (p less than 0.05) and less biased than those obtained with the standard Vd. The precision of prediction based on individual Vd values was quantitatively similar (root mean squared error = 3.38 mg/L) to reported predictions based on pharmacokinetic values derived from an initial intravenous course of aminophylline therapy. We conclude that theophylline dosage requirements can be accurately estimated from orally derived pharmacokinetic data and that the method described may be useful for patients in whom intravenous therapy is not required or contraindicated.
利用口服获得的药代动力学数据和一级吸收方程,对34例年龄在0.25至14.8岁的儿科患者进行了常规释放型口服茶碱的需求量测定。半衰期(2.3 - 21.3小时)和计算得出的表观分布容积(Vd)(0.300 - 1.54升/千克)范围较大。当使用个体患者的Vd值计算时,平均血清茶碱浓度与实际平均浓度的相关性更强(r = 0.61,p小于0.0002),而使用0.5升/千克的标准Vd计算时相关性较弱(r = 0.31,无显著性差异),并且使用个体Vd值获得的预测更精确(p小于0.05),偏差也比使用标准Vd时更小。基于个体Vd值的预测精度在定量上与基于氨茶碱治疗初始静脉给药过程中获得的药代动力学值所报告的预测相似(均方根误差 = 3.38毫克/升)。我们得出结论,茶碱的剂量需求可以根据口服获得的药代动力学数据准确估算,并且所描述的方法可能对不需要或禁忌静脉治疗的患者有用。