Gram L F, Schmidt K, Christensen F N, Schou J
Eur J Clin Pharmacol. 1984;26(6):749-52. doi: 10.1007/BF00541937.
Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model. Analysis of residuals (difference between observed and computed concentrations) revealed similar systematic deviations in all 8 subjects when the 2-compartment model was used (5-10 h negative residuals, after 13 h positive residuals). In contrast, curve-fit by a 3-compartment model (with two parallel peripheral compartments) was good with no systematic deviations. The data show that a terminal monoexponential decline in d-propoxyphene concentrations cannot be expected until 15-30 h after single dose administration, and that the determination of the corresponding half-life is rather inaccurate. Accordingly, precise steady state level predictions may be difficult to obtain from conventional single dose studies with d-propoxyphene.
先前发表的一项对8名健康受试者静脉注射65毫克右旋丙氧芬单剂量研究的数据，已通过曲线拟合程序进行非线性回归分析，以测试二室和三室开放模型的适用性。残差分析（观测浓度与计算浓度之间的差异）显示，当使用二室模型时，所有8名受试者都存在类似的系统偏差（5 - 10小时为负残差，13小时后为正残差）。相比之下，三室模型（有两个平行外周室）的曲线拟合良好，没有系统偏差。数据表明，单剂量给药后15 - 30小时之前，不能预期右旋丙氧芬浓度呈终末单指数下降，并且相应半衰期的测定相当不准确。因此，从传统的右旋丙氧芬单剂量研究中可能难以获得精确的稳态水平预测。
