Sandström M, Lindman H, Bergh J and Karlsson M O.
Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences and Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
The effectivity of the anthracycline epirubicin and the taxane docetaxel when given as single drugs has resulted in the introduction of the combination therapy into the clinic. The pharmacokinetics of the drugs when given in combination have been described but until now there has been no characterization of the PK-PD relationships. The aim of this study was to characterize the relationships between the pharmacokinetics and the dose limiting haematological toxicity as well as other side-effects of the epirubicin-docetaxel regimen. The side-effects were monitored in 43 patients during 297 dosing occasions. In sixteen of those patients the pharmacokinetics of epirubicin and docetaxel were investigated. The data analysis was made in NONMEM version VI. In the pharmacokinetic analysis, the option to use prior information in the analysis was used. The relationships between the exposure of the component drugs and the side-effects were investigated. The development of haematological toxicity was well described with a semi-physiological model.
Reference: PAGE 10 (2001) Abstr 221 [www.page-meeting.org/?abstract=221]
Poster: poster