title: Intravenous cereport (RMP-7) enhances delivery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tumors in the brain.
abstract: OBJECTIVE
  The following experiments determined whether intravenous infusions of Cereport enhance delivery of chemotherapeutics and prolong survival in rats with metastatic tumors in the brain.
  
  
  METHODS
  Autoradiography and scintillation were used to examine uptake of the lipophilic (paclitaxel and carmustine) and the hydrophilic (carboplatin) chemotherapeutic agents, as well as the large hydrophilic marker, 70 kDa dextran. Cereport was also tested in combination with the chemotherapeutic drugs carboplatin, vinorelbine, gemcitabine and carmustine to determine if Cereport could enhance the survival benefit beyond that provided by chemotherapy alone.
  
  
  RESULTS
  Cereport enhanced the uptake of carboplatin and dextran, but not paclitaxel or carmustine. The pattern of Cereport's uptake effect with carboplatin revealed that Cereport selectively increased the proportion of highly permeable regions. Survival was significantly enhanced when Cereport was combined with either carboplatin, vinorelbine, or gemcitabine, but not carmustine, compared to each chemotherapeutic agent alone.
  
  
  CONCLUSIONS
  These data provide the first evidence that Cereport, or any receptor-mediated approach intended to enhance the permeability of the blood-brain tumor barrier, can increase the delivery hydrophilic drugs to metastatic tumors in the brain, increasing survival in tumor-bearing rats.
authors.affiliation: Alkermes, Inc, Cambridge, Massachusetts, USA. dwaine.emerich@alkermes.com
authors.forename: D F
authors.initials: DF
authors.lastname: Emerich
authors.forename: R L
authors.initials: RL
authors.lastname: Dean
authors.forename: J
authors.initials: J
authors.lastname: Marsh
authors.forename: M
authors.initials: M
authors.lastname: Pink
authors.forename: D
authors.initials: D
authors.lastname: Lafreniere
authors.forename: P
authors.initials: P
authors.lastname: Snodgrass
authors.forename: R T
authors.initials: RT
authors.lastname: Bartus
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D016190:Carboplatin / Q000493:pharmacokinetics / Q000494:pharmacology; D002330:Carmustine / Q000493:pharmacokinetics / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; C089876:RMP 7; D014747:Vinblastine; D016190:Carboplatin; D000077235:Vinorelbine; D001920:Bradykinin; D002330:Carmustine; D000093542:Gemcitabine