Chrystyn H, Ellis J W, Mulley B A, Peake M D
School of Pharmacy, Bradford University, West Yorkshire, England.
Ther Drug Monit. 1988;10(3):299-305. doi: 10.1097/00007691-198803000-00011.
Pharmacokinetic parameters for theophylline were determined in 33 patients (3 women), mean age 61.2 years and weight 74.6 kg using the following three methods: (a) standard one-compartmental model calculations, assuming 100% bioavailability, after a single dose of theophylline syrup (mean dose 413 mg); (b) drug nomogram; and (c) Bayesian analysis. Patients entered a randomised study of three two-monthly dosage regimens using low, medium, and high theophylline twice daily doses. These doses produced mean (+/- SE) steady-state serum theophylline concentrations of 6.3 (+/- 0.4), 12.1 (+/- 0.3) and 18.3 (+/- 0.5) mg/L, respectively. A fourth period of placebo (2-month duration) was also included. At the end of each treatment period the measured serum theophylline concentration of each patient was compared with those predicted by each of the above three methods. The revised estimates derived from Bayesian analysis produced the least biased [mean prediction error (ME)] and most precise (mean squared prediction error) predictions for all three dosage periods. Statistical analysis of relative performance demonstrated that the difference in precision between the revised estimates and those of the other two methods was significant (p less than 0.05) with the magnitude of the difference increasing with dose. The revised estimates were also found to be less biased (p less than 0.05) than those of the nomogram. The ME (+/- SE) of the revised estimates for the low, medium, and high dosage periods was 0.34 (+/- 0.30), -0.02 (+/- 0.22) and -0.48 (+/- 0.31) mg/L, respectively.
采用以下三种方法测定了33例患者（3名女性）的茶碱药代动力学参数，患者平均年龄61.2岁，体重74.6kg：(a) 标准一室模型计算法，单剂量给予茶碱糖浆（平均剂量413mg）后，假设生物利用度为100%；(b) 药物剂量图表法；(c) 贝叶斯分析法。患者进入一项随机研究，该研究采用三种每两个月一次的给药方案，每日两次给予低、中、高剂量的茶碱。这些剂量分别产生平均（±标准误）稳态血清茶碱浓度为6.3（±0.4）、12.1（±0.3）和18.3（±0.5）mg/L。还包括一个为期2个月的安慰剂治疗期。在每个治疗期结束时，将每位患者测得的血清茶碱浓度与上述三种方法预测的浓度进行比较。贝叶斯分析得出的修正估计值在所有三个给药期的预测中偏差最小[平均预测误差(ME)]且最为精确（均方预测误差）。相对性能的统计分析表明，修正估计值与其他两种方法的精度差异显著（p<0.05），且差异幅度随剂量增加而增大。还发现修正估计值的偏差也小于剂量图表法（p<0.05）。低、中、高剂量期修正估计值的ME（±标准误）分别为0.34（±0.30）、-0.02（±0.22）和-0.48（±0.31）mg/L。
