Pharmacokinetics of intracarotid artery 14C-BCNU in the squirrel monkey.

A comparison of intravenous to intracarotid artery (ICA) administration of 14C-BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) was made in squirrel monkeys. Radioactivity was measured as soluble drug products and as RNA-, DNA-, and protein-bound radioactivity. The ICA administration of BCNU achieved 190% to 280% higher brain nucleic acid-bound drug levels than use of the intravenous route in the infused hemisphere and 130% to 280% higher levels than in the noninfused hemisphere.

Relationship of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) pharmacokinetics of uptake, distribution, and tissue/plasma partitioning in rat organs and intracerebral tumors.

To obtain a clearer definition of the relationship between the structure of BCNU and CCNU and their antitumor activity, we determined the uptake, distribution, and tissue/plasma partition ratios of both compounds in normal organs and intracerebral (ic) 9L tumors in rats. Greater uptake, distribution, and tissue/plasma partition ratios were obtained for parent CCNU in fat, liver, and brain, and for parent BCNU in kidney. CCNU distributes more rapidly and extensively than BCNU only in fatty tissues.

Dianhydrogalactitol (NSC-132313): pharmacokinetics in normal and tumor-bearing rat brain and antitumor activity against three intracerebral rodent tumors.

Dianhydrogalactitol (DAG; NSC-132313), a hexitol epoxide, was used to treat intracerebral rodent tumors. DAG was most active against the murine ependymoblastoma [treated/controls (T/C)greater than 440%], less active against murine glioma 26 (T/C approximately 112-150%), and least active against rat 9L gliosarcoma (T/C approximately 100%). Application of a two-compartment open model for plasma disappearance of 14C-DAG in rats gave a volume of distribution at steady state of approximately 872 ml, a clearance of approximately 9.

Permeability characteristics of brain adjacent to tumors in rats.

The brain immediately surrounding 9L sarcoma and Walker 256 carcinosarcoma was evaluated, using radioactive water, albumin, red blood cells, urea, and sodium to quantitate isotopic exchange and permeability in the brain adjacent to tumor (BAT), normal brain, and, to a lesser extent, tumor. Exchange between blood and BAT for 14C-urea and 22Na averaged 53% of that for comparable regions of normal brain. This reduction in exchange is not explainable by differences in capillary surface area for transcapillary exchange in the BAT.