title: Steroids decrease uptake of carboplatin in rat gliomas--uptake improved by intracarotid infusion of bradykinin analog, RMP-7.
abstract: This study sought to determine whether dexamethasone (DXN) treatment of rats with intracranial gliomas would 1) further impair delivery of carboplatin to brain tumors, and 2) whether intracarotid infusion of the bradykinin analog, RMP-7, would improve delivery during concurrent DXN treatment. In DXN pretreated animals, 3 mg/kg/day of DXN was administered intraperitoneally for 3 days prior to Ki determinations. Ki of [14C] carboplatin into DXN-treated tumors and brain surrounding tumor (BST) was significantly lower compared to non-DXN treated tumors and BST (3.30 +/- 0.91 vs. 4.47 +/- 1.80, p < 0.05, and 0.94 +/- 0.84 vs. 2.18 +/- 0.79, p < 0.05, respectively). Intracarotid infusion of RMP-7 significantly increased the Ki for carboplatin in DXN-treated tumors (6.35 +/- 3.10 vs. 3.30 +/- 0.91, p < 0.01), however, RMP-7 increased Ki to a greater extent in tumors not pretreated with DXN (12.07 +/- 3.60 vs. 4.47 +/- 1.80, p < 0.0001). Dexamethasone decreases transport of carboplatin into brain tumors. Intracarotid infusion of RMP-7 selectively increases carboplatin transport to tumors.
authors.affiliation: Jonsson Comprehensive Cancer Center, Division of Neurosurgery, UCLA Medical Center, USA.
authors.forename: K
authors.initials: K
authors.lastname: Matsukado
authors.forename: S
authors.initials: S
authors.lastname: Nakano
authors.forename: R T
authors.initials: RT
authors.lastname: Bartus
authors.forename: K L
authors.initials: KL
authors.lastname: Black
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016190:Carboplatin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D002339:Carotid Arteries; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids; C089876:RMP 7; D003907:Dexamethasone; D016190:Carboplatin; D001920:Bradykinin