诺模图法预测口服给药的吸收速率常数

Development of A Nomogram that Estimate The Absorption Rate Coefficient after Oral Administration

目的:用已知的达峰时间(t_(peak))和消除速率常数(k_e)建立诺模法,估算口服给药的吸收速率常数(K_a)。方法:根据口服给药的血药浓度-时间曲线曲线方程和t_(peak)、k_a和k_e的函数关系,进行数学推导建立诺模图。应用诺模图分析46个药物的k_a与数学解析法计算的k_a,比较评价诺模图的准确度。用高效液相色谱荧光法检测18位健康志愿者羧甲司坦的血药浓度,将羧甲司坦实测血药浓度与由k_a结合其他药代动力学参数的估计血药浓度比较,评估诺模图执行误差。结果:诺模图估算的k_a值与解析法计算的k_a值接近;MDPE和MDAPE执行误差分别为1.32％,18.15％。结论:本文设计的诺模图准确可靠,执行误差符合临床药代动力学要求。可为制定合理的个体化给药方案提供一个方便快捷的方法。

OBJEIVE A simple nomogram was construed to estimate the absorption rate coefficient (Ka) using the peak time (tpeak) and the elimination rate coefficient (ke) of drugs administered orally. METHOD The nomogram was based on the plasma concentration-time curve and the funion relation between tpeak,ka and ke. A mathematical analysis was presented which allowed for the construion of single chart nomogram. To check on the degree of accuracy of the developed nomogram. It was used to analyze retrospeive profiles of 46 drugs and compared the ka alues from nomogram and those calculated by solving the equation. To analyze the performance error, the measured carbocisteine concentrations were compared with the predied concentrations by ka from the nomograms along with the other pharmacokinetic parameters. RESULTS The estimations of ka values from nomogram were in very close proximity with the numerical values. The performance error was as follow MDPE and MDAPE are 1.3% and 18.2%, respeively. CONCLUSION The developed nomogram is accurate and reliable. The sive of performance error meets the demand of clinical pharmacokinetics. The nomograms may offer another convenient and easy method for rational individualized dosage regimen.