Population Pharmacokinetics and Pharmacodynamics of Doxorubicin and Cyclophosphamide in Breast Cancer Patients

Abstract

The proposed inhibitory population pharmacokinetic-pharmacodynamic model adequately described individual neutrophil counts after administration of doxorubicin and cyclophosphamide. In this patient population, exposure to cyclophosphamide, as assessed by the AUC, might have been a predictor of the treatment response, whereas exposure to doxorubicin was not. A prospective study should validate cyclophosphamide exposure as a predictive marker for the treatment response and clinical outcome in this patient group.

Population pharmacokinetics of doxorubicin: establishment of a NONMEM model for adults and children older than 3 years

“…From all five studies performing analyses with NONMEM Ò [5,18,19,31,34], the full pharmacokinetic datasets were available for the present analysis. One trial was excluded from the outset since it investigated a specific population with high comorbidity and bad performance score [18].…”

“…One trial was excluded from the outset since it investigated a specific population with high comorbidity and bad performance score [18]. The datasets of Callies et al [5], Thompson et al [31] and Wilde et al [34] were used for model building, and the dataset of Jörger et al [19] served for an external model evaluation.…”

“…Pij values should be uniformly distributed between 0 and 1. Dataset 4 was used for an external model evaluation [19]. It contained 232 doxorubicin and 196 dox'ol plasma concentrations of 59 females (30-81 years).…”

“…Analyses of the plasma samples were performed by high-performance liquid chromatography and fluorescence detection (limit of quantification 1 lg/L). The final model was applied to dataset 4, and parameter estimates were compared to the doxorubicin and dox'ol pharmacokinetic parameters from the analysis of the other datasets [19].…”

Pharmacogenetics of Human Carbonyl Reductase 1 (CBR1) in Livers from Black and White Donors

“…In addition, Joerger et al (2007) detected a negative correlation between the clearance of doxorubicin and age by using a physiologically based pharmacokinetic model. They concluded that a 10-year increase in patient age led to a 9% decrease in doxorubicin clearance (Li and Gwilt, 2003;Joerger et al, 2007). In this study, we detected a significant negative correlation between age and maximal CBR activity in samples from whites (r p ϭ Ϫ0.439; p ϭ 0.006).…”