Extracorporeal hemofiltration: a model for decreasing systemic drug exposure with intra-arterial chemotherapy.
Cisplatin (3 mg/kg) was infused through the hepatic artery in nine mongrel dogs. Four of these dogs underwent simultaneous extracorporeal hemofiltration (ECH) of the hepatic venous effluent using a high-flow, dual-lumen catheter placed in the vena cava at the level of the hepatic veins. Platinum levels were measured in the plasma, urine, and ultrafiltrate and in kidney and liver tissue. ECH significantly reduced systemic drug exposure as measured by the AUC for free and total platinum, by urinary excretion, and by 24-h kidney levels. Regional liver levels were minimally affected. Recovery of platinum in the ultrafiltrate was 40% +/- 14%. ECH resulted in efficient extraction of platinum and reduced systemic drug exposure with relative preservation of regional hepatic drug exposure.
Graham
R A
RA
Department of General Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Siddik
Z H
ZH
Hohn
D C
DC
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D004285:Dogs; D006440:Hemofiltration / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage; D006499:Hepatic Artery; D006503:Hepatic Veins; D007261:Infusions, Intra-Arterial / Q000379:methods*; D008099:Liver / Q000032:analysis / Q000378:metabolism; D010984:Platinum / Q000032:analysis / Q000493:pharmacokinetics; D013997:Time Factors
D010984:Platinum; D006493:Heparin; D002945:Cisplatin