Pharmacokinetics of platinum in cancer patients treated with carboplatin in combination with high-dose methotrexate.
The pharmacokinetics of platinum was investigated in 10 cancer patients treated with a 1-hr infusion of 300 mg/m2 of carboplatin which was given 2-4 days after the administration of 100 mg/kg (20-mg/kg bolus and 80-mg/kg intravenous infusion) of methotrexate. Platinum was analyzed in the samples by flameless atomic absorption spectrophotometry. The concentration vs time data for total platinum in plasma followed a two-compartment model and the mean (and SE) values for beta, TBC, Vc, and RC were 0.0827 (0.22) hr-1, 2.355 (0.252) liters/hr . m2, 10.74 (0.62) liters/m2, and 2.405 (0.228) liters/hr . m2, respectively. There was no significant change in the creatinine clearance or TBC with repeated treatment. The ultrafilterable platinum which was measured in the plasma of two patients constituted 82 and 11.3% of the total platinum at 1 and 24 hr, respectively, and the data conformed to the one-compartment model. The mean (SE) values for t 1/2, TBC, and Vd for free platinum were 1.844 (0.208) hr, 4.583 (1.059) liters/hr . m2, and 11.88 (1.45) liters/m2, respectively. The above data are in good agreement with those reported earlier for platinum following the administration of carboplatin as a single agent. These results suggest that high-dose methotrexate therapy, when administered 2-4 days before carboplatin, does not affect the pharmacokinetics of platinum in the plasma.
el-Yazigi
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A
Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Amer
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M
Martin
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CR
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016190:Carboplatin; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D010984:Platinum / Q000493:pharmacokinetics* / Q000652:urine; D013054:Spectrophotometry, Atomic; D014462:Ultrafiltration
D009944:Organoplatinum Compounds; D010984:Platinum; D003404:Creatinine; D016190:Carboplatin; D008727:Methotrexate