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. In addition, some brain regions directly subserved by the middle cerebral artery had bound drug levels four- to fivefold greater than those found in regions of noninfused brain. The data suggest that a need for BCNU dose reduction due to myelotoxicity may be an indication for ICA therapy in selected brain-tumour cases.