Disposition of cyclophosphamide on two consecutive cycles of treatment in patients with ovarian carcinoma.
The disposition of cyclophosphamide was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, doxorubicin (adriamycin) 50 mg/m2 and cisplatin 50 mg/m2 during their first and second courses of therapy. Plasma samples were obtained over 24 h following the completion of the cyclophosphamide infusion and assayed for cyclophosphamide by high performance liquid chromatography. The mean disposition of cyclophosphamide conformed to a 2-compartment model with a mean terminal half-life of 7.14 h on the first course and 8.77 h on the second course. Mean area under the plasma concentration versus time curve appeared to increase from 248.8 mg.h/l for the initial course to 282.2 mg.h/l on the second. Mean total body clearance was 2.01 l/h/m2 on the first course and 1.77 l/h/m2 on the second. Volume of distribution on the first and second courses were 15.3 l/m2 and 18.1 l/m2, respectively. These results suggested that cyclophosphamide clearance decreased when given in a bolus fashion every 3 weeks. However, inter-patient and intra-patient variability was large and the differences in the calculated parameters were not statistically significant when the individual patient data was considered. It is concluded that: 1. cyclophosphamide disposition can best be fit by a bi-exponential equation; 2. considerable intra- and interpatient variability in the concentration-time profile will be encountered; 3. cyclophosphamide disposition does not change from the first to the second course. Reasons for the wide variation are proposed.
Erlichman
C
C
Department of Medicine, University of Toronto, Ontario, Canada.
Soldin
S J
SJ
Hardy
R W
RW
Thiessen
J J
JJ
Sturgeon
J F
JF
Fine
S
S
Baskerville
T
T
D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D003520:Cyclophosphamide