Infusion rates and drug distribution in brain tumor models in rats.
OBJECTIVE
The aim of this study was to investigate the optimal delivery rates of chemotherapy for the treatment of central nervous system tumors and to determine whether local delivery can lower toxicity profiles and increase target concentrations of chemotherapy.


METHODS
The authors used two brain tumor models in rats. Slow (1 microl/hour) and fast (10 microl/hour) pumps were used to deliver chemotherapy--carboplatin, doxorubicin, and a high-molecular-weight transferrin-doxorubicin conjugate to the brains of normal rats and rats previously injected with F98 or 9L rat brain tumor cells. Brains were cut in 1-mm sections rostral and caudal from the infusion point. Slices were analyzed for doxorubicin and platinum by fluorescence and atomic absorption, respectively. In the normal tissues, the volume of drug distribution is generally greater at the faster flow rate. In abnormal tissues, distribution is similar at slow and fast infusion rates for low-molecular-weight drugs and greater at slow rates for a high-molecular-weight targeted toxin.


CONCLUSIONS
After local administration the distribution of chemotherapy appears to be significantly influenced by tumor metabolism. Additional studies are needed to determine the optimal delivery rates for the interaction of the drug with the targeted tumor.
Khan
Andleeb
A
Division of Pediatric Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland 21287-8811, USA.
Jallo
George I
GI
Liu
Ya J
YJ
Carson
Benjamin S
BS
Guarnieri
Michael
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000662:veterinary; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D007260:Infusion Pumps; D008970:Molecular Weight; D051381:Rats; D011916:Rats, Inbred F344; D014168:Transferrin / Q000008:administration & dosage / Q000493:pharmacokinetics
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D014168:Transferrin; D004317:Doxorubicin; D016190:Carboplatin