Influence of infusion time on unchanged cisplatin disposition in patients with ovarian cancer.
The disposition of unchanged cisplatin in ten patients with ovarian cancer receiving 2-h infusions of 100 mg/m2 was compared with that of ten patients receiving 6-h infusions. A high-performance liquid chromatographic assay specific for the unchanged drug was used and all collected samples were rapidly processed. Patients were catheterized for urine collections. Cisplatin renal clearance was significantly lower after 6-hour infusions (52.8 +/- 16.2 ml/min per m2) than after 2-h infusions (87.1 +/- 38.2 ml/min per m2) (P = 0.026). Total clearance was also lower and less variable, although not significantly, in patients receiving the longer infusion. No differences in nonrenal clearance, volume of distribution, or half-life were observed between the two groups. There was only a poor relationship between cisplatin renal clearance and creatinine clearance after 2-h (r2 = 0.02; P = 0.66) and 6-h infusions (r2 = 0.18; P = 0.23). A single cisplatin plasma level obtained at the end of the infusion proved to be a good predictor of total cisplatin clearance after both 2-h (r2 = 0.70; P = 0.0096) and 6-h infusions (r2 = 0.97; P = 0.0001). This level was not significantly related to the relatively small changes in creatinine clearance that occurred after three courses of treatment.
Reece
P A
PA
Department of Clinical Pharmacology, Queen Elizabeth Hospital, Adelaide, Australia.
Stafford
I
I
Davy
M
M
Morris
R
R
Freeman
S
S
D000368:Aged; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003404:Creatinine / Q000652:urine; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D003404:Creatinine; D002945:Cisplatin