TY - JOUR T1 - Pyrimidine dideoxyribonucleosides: selectivity of penetration into cerebrospinal fluid. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 466 LP - 470 VL - 245 IS - 2 AU - J M Collins AU - R W Klecker, Jr AU - J A Kelley AU - J S Roth AU - C L McCully AU - F M Balis AU - D G Poplack Y1 - 1988/05/01 UR - http://jpet.aspetjournals.org/content/245/2/466.abstract N2 - Cerebrospinal fluid (CSF)/plasma ratios of 1 to 30% were obtained in rhesus monkeys for the 3'-azido- and 2',3'-dideoxy-analogs of thymidine, deoxycytidine and deoxyuridine. Penetration of thymidine and deoxyuridine analogs was much greater than for deoxycytidine analogs. Octanol/buffer partition coefficients varied more than 30-fold, but did not correlate with CSF entry. Plasma protein binding was insignificant for all compounds. The presence or absence of the azido group at position 3' did not appear to influence the extent of CSF penetration. Although we do not fully understand the mechanistic basis for the penetration of these nucleosides into the CSF, it is apparent that the structural specificity is related more closely to the nucleobase than the sugar. Based upon elimination rates from the CSF after direct intrathecal injection, the differences in net penetration are determined by influx rather than efflux processes. ER -