Oxaliplatin pharmacokinetics during a four-hour infusion.
A new platin compound, oxaliplatin, has significant activity in advanced colorectal carcinomas. However, its pharmacokinetics have not been characterized adequately yet. This study extensively analyzes the pharmacokinetics of both ultrafiltrable (free) and protein-bound platin in 13 patients receiving 130 mg/m2 oxaliplatin as a 4-h infusion in combination with 375 mg/m2 5-fluorouracil as a 24-h infusion for advanced colorectal carcinomas. The interpatient variability was very low for all parameters analyzed. The levels of free platin decreased triphasically, with a mean terminal half-life of 27.3+/-10.6 h. The area under the time-concentration curve was 20.17+/-6.97 microg.h/ml and the total and renal clearances amounted to 222+/-65 and 121+/-56 ml/min, respectively. The values for the volume of distribution and for the maximum concentration at the end of infusion were 349+/-132 liters and 1612+/-553 ng/ml, respectively. On the basis of the simulation of the plasma levels and the urinary excretion of platin following the long-term administration of oxaliplatin as a constant-rate and a chronomodulated infusion, additional analyses are warranted to fully characterize the pharmacokinetics of the drug in these settings.
Kern
W
W
Ludwig-Maximilians-University Hospital Grosshadern, Department of Medicine III, München, Germany. wolfgang.kern@med3.med.uni-muenchen.de
Braess
J
J
Böttger
B
B
Kaufmann
C C
CC
Hiddemann
W
W
Schleyer
E
E
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002277:Carcinoma / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003198:Computer Simulation; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D008954:Models, Biological; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000077150:Oxaliplatin
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil