Pharmacokinetic properties of doxorubicin encapsulated in glutaraldehyde-treated canine erythrocytes.
Canine erythrocytes were loaded with the antineoplastic drug doxorubicin and then treated with 0.16% glutaraldehyde. This procedure has been previously shown to slow down the efflux of doxorubicin from erythrocytes and to result in the selective targeting of the carrier erythrocytes to liver. Three dogs were treated each with 2 different schedules of IV bolus administration of doxorubicin (0.4 mg/kg of body weight): free drug and doxorubicin encapsulated in glutaraldehyde-treated erythrocytes. The 2 treatments yielded consistent differences in the plasma pharmacokinetic properties of doxorubicin and of its only metabolite, doxorubicinol. A triphasic exponential decay of doxorubicin plasma concentrations was observed on injection of the free drug. Conversely, in the case of erythrocyte-encapsulated doxorubicin, 4 phases of plasma concentrations of doxorubicinol were found. The plasma concentrations of doxorubicinol, after a steady increase during the first hour, followed patterns of decay comparable to those of the parent drug. On the basis of the kinetic variables calculated with the 2 administration schedules, area under curve concentrations of plasma doxorubicin were 136 micrograms.h/L (free infusion) and 734 micrograms.h/L (erythrocyte-encapsulated drug). Significant alterations of hematologic and hematochemical factors were not observed in the 3 dogs during and after the 2 treatments. On the basis of our findings, doxorubicin-loaded and glutaraldehyde-treated erythrocytes may potentially be used in the treatment of systemic and hepatic tumors in dogs.
Tonetti
M
M
Institute of Biochemistry, University of Genoa, Italy.
Astroff
A B
AB
Satterfield
W
W
De Flora
A
A
Benatti
U
U
DeLoach
J R
JR
D000818:Animals; D004285:Dogs / Q000097:blood / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004912:Erythrocytes / Q000187:drug effects*; D005976:Glutaral / Q000494:pharmacology*; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary
D004317:Doxorubicin; D005976:Glutaral