Comparative pharmacokinetics of doxorubicin given by three different schedules with equal dose intensity in patients with breast cancer.
The pharmacokinetics of doxorubicin given according to three different schedules with a similar dose-time intensity have been studied and compared in 16 women with metastatic breast cancer. Six patients were treated with doxorubicin 75 mg/m2 by i.v. bolus repeated every 3 weeks; 5 patients received doxorubicin by 4-day continuous infusion every 3 weeks (4 at 75 mg/m2 and 1 at 60 mg/m2); 5 patients received 25 mg/m2 by i.v. bolus given weekly. Timed blood samples were collected and plasma levels of doxorubicin and its metabolite doxorubicinol were measured by high-performance liquid chromatography with fluorescence detection. Peak plasma concentrations were measured, and areas under the concentration-time curves calculated. Peak plasma levels of doxorubicin were significantly lower with the 4-day infusion than with either of the bolus injections. The 4-day infusion, however, gave significantly greater total exposure to doxorubicin and doxorubicinol, as indicated by area under the concentration-time curve, than weekly or 3-weekly bolus treatment. A single bolus injection of doxorubicin 25 mg/m2 yielded a total exposure to doxorubicin approximately half that achieved with a 75 mg/m2 bolus injection. Over a 3-week period, therefore, total exposure to doxorubicin would be greater with the weekly low-dose schedule than with the 3-weekly administration. We conclude that drug scheduling has significant effects on doxorubicin pharmacokinetics.
Twelves
C J
CJ
Division of Oncology, UMDS, Guy's Hospital, London, England.
Dobbs
N A
NA
Aldhous
M
M
Harper
P G
PG
Rubens
R D
RD
Richards
M A
MA
D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D009362:Neoplasm Metastasis; D013997:Time Factors
D004317:Doxorubicin; C010013:adriamycinol