Hepatic intra-arterial administration of doxorubicin and degradable starch microspheres. A pharmacokinetic study in the rat.
Urinary concentration of doxorubicin and its active metabolite doxorubicinol was followed in two groups of rats after hepatic intra-arterial injection of a single dose of 6 mg/kg doxorubicin or the same dose combined with 30 mg/kg Spherex (DSM). Urinary samples were collected during five days following administration. The concomitant DSM administration caused a significant decrease of the cumulative urinary excretion of intact doxorubicin; average five days of cumulative values were 73 and 103 micrograms respectively in the group with and without DSM. This indicates a DSM-induced reduction in systemic drug exposure. The elimination rates of doxorubicin or its active metabolite were not influenced by DSM. The decrease in excretion of the parent drug was not due to an interaction between the drug and DSM as evident by examining the binding of doxorubicin to DSM in vitro. Instead regionally altered drug distribution seems a plausible explanation to the reduction.
Johansson
C J
CJ
Kabi Pharmacia AB, Therapeutics Oncology Dept. of Pharmacokinetics, Helsingborg, Sweden.
Teder
H
H
Grönquist
L
L
Gunnarsson
P O
PO
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D004359:Drug Therapy, Combination; D007261:Infusions, Intra-Arterial; D008102:Liver Circulation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013213:Starch / Q000008:administration & dosage*
D004317:Doxorubicin; C044817:Spherex; D013213:Starch; C010013:adriamycinol