Abstract | PURPOSE: PATIENTS AND METHODS: Data from 21 women were collected over a total of 35 cycles. 5-FU (300 to 600 mg/m2) and CP (300 to 600 mg/m2) were administered as bolus injections, whereas EPI (15 to 60 mg/m2) was administered either as a bolus injection or as an infusion. The pharmacokinetics of the component drugs were monitored using a limited sampling scheme. Population pharmacokinetic models for each of the three drugs were developed using the program NONMEM. RESULTS: The data for 5-FU were best described by a one-compartment model with nonlinear elimination, where the maximal rate of elimination (Vmax) and the concentration at which the elimination was half-maximal (Km) were 105 mg/L.h and 27 mg/L, respectively. EPI concentration-time profiles showed a triexponential decline, with a mean terminal half-life of 24 hours and a clearance (CL) of 59 L/h. The elimination of 4-OHCP was monoexponential, with a mean half-life of 7 hours. The interindividual coefficients of variation (CVs) in CL were 30%, 22%, and 41% for 5-FU, EPI, and 4-OHCP, respectively. The corresponding values for intrapatient course-to-course variability in CL were 11%, 8%, and 27%. No significant correlation in any of the pharmacokinetic parameters between the drugs was found. CONCLUSION: Individualization of dosing of the FEC regimen using therapeutic drug monitoring and attempts to find concentration-response relationships may be successful, but requires that the exposure of all three drugs is considered simultaneously.
|
Authors | M Sandström, A Freijs, R Larsson, P Nygren, M L Fjällskog, J Bergh, M O Karlsson |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 14
Issue 5
Pg. 1581-8
(May 1996)
ISSN: 0732-183X [Print] United States |
PMID | 8622075
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- 4-hydroxycyclophosphamide
- Epirubicin
- Cyclophosphamide
- Fluorouracil
|
Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(pharmacokinetics, therapeutic use)
- Breast Neoplasms
(drug therapy, metabolism)
- Cyclophosphamide
(administration & dosage, analogs & derivatives, blood, pharmacokinetics)
- Epirubicin
(administration & dosage, pharmacokinetics)
- Female
- Fluorouracil
(administration & dosage, pharmacokinetics)
- Half-Life
- Humans
- Middle Aged
|