Hepsulfam distribution in blood, plasma and cerebrospinal fluid of baboons.

The alkylating agent Hepsulfam (Sulfamic acid 1,7-heptanediyl ester, NSC 329680) was developed as a more hydrophilic analog of busulfan. The objective of this study was to determine partitioning of hepsulfam between blood, plasma, and cerebrospinal fluid (CSF) in two female baboons following intravenous administration. Hepsulfam was administered at 11 mg/kg, and blood and CSF levels were determined by gas chromatography with electron capture detection. Blood levels were fairly constant between animals (17-25 and 20-23 micrograms/ml) for six hours after administration, following peak levels of 43 and 33 micrograms/ml, respectively, for the two animals. Peak plasma levels of 35 and 36 micrograms/ml were achieved, and initial plasma half-lives in baboons were similar to those seen in other species, with a t1/2 alpha of 1 h. The plasma terminal half life of 0.2 h, estimated from limited sampling times, was shorter in baboons than in mice, dogs, or humans. Baboon CSF levels decreased from 1.7 to 0.3 micrograms/ml during 6 h post infusion, and peak concentrations in CSF lagged behind plasma levels. CSF/plasma ratios ranged from 0.33 to 0.62 in one animal, whereas ratios of 0.2-0.25 were maintained in the other animal during the same period. Results from this study indicate hepsulfam will enter the CSF following intravenous administration, and the CSF/plasma ratios are lower than those obtained following oral busulfan administration.