Comparative effects of paclitaxel and docetaxel on the metabolism and pharmacokinetics of epirubicin in breast cancer patients.
OBJECTIVE
To investigate whether paclitaxel and docetaxel influence the pharmacokinetics and metabolism of epirubicin.


METHODS
We studied the pharmacokinetics and biotransformation patterns of epirubicin in 27 cycles and 20 breast cancer patients. Four patients received epirubicin alone 90 mg/m(2) by intravenous (IV) bolus; eight patients received the same dose of epirubicin followed immediately by paclitaxel 175 mg/m(2) in a 3-hour infusion; the other eight patients received epirubicin 90 mg/m(2) followed immediately by docetaxel 70 mg/m(2) in a 1-hour infusion. Epirubicin and its metabolites, epirubicinol (EOL) and 7-deoxydoxorubicinone (7d-Aone), were identified by high-pressure liquid chromatography.


RESULTS
No pharmacokinetic interaction between the parent compound epirubicin and taxanes was detected. Conversely, a significant effect on epirubicin metabolism by both paclitaxel and docetaxel was found. Epirubicin given with paclitaxel or docetaxel yielded areas under the plasma concentration-time curves (AUC) for 7d-Aone 1. 7-fold and 1.9-fold higher (P <.05), respectively, than epirubicin alone. The appearance of two polar metabolites sensitive to glucuronidase was also significantly greater in both taxane groups. Quantitatively different metabolic rates and patterns for EOL were observed in the paclitaxel and docetaxel combinations. The EOL AUC after paclitaxel treatment (1,521 +/- 150 ng/mL*h) was significantly higher (P <.01) than the corresponding values after epirubicin administered either as a single agent (692 +/- 46 ng/mL*h) or in combination with docetaxel (848 +/- 237 ng/mL*h).


CONCLUSIONS
There is no apparent pharmacokinetic interaction between the parent compound epirubicin and paclitaxel or docetaxel. A different pattern of interaction between these taxanes and epirubicin metabolism is clearly evident.
Esposito
M
M
Pharmacotoxicology Laboratory, Department of Preclinical Oncology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. mventur@hp380.ist.unige.it
Venturini
M
M
Vannozzi
M O
MO
Tolino
G
G
Lunardi
G
G
Garrone
O
O
Angiolini
C
C
Viale
M
M
Bergaglio
M
M
Del Mastro
L
L
Rosso
R
R
D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D019540:Area Under Curve; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D000077143:Docetaxel; D004357:Drug Synergism; D015251:Epirubicin / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D043823:Taxoids
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D017239:Paclitaxel