Pharmacokinetic and metabolic studies of busulfan in rat plasma and brain

Abstract

Busulfan kinetics were studied in the rat plasma and brain after an I.P. dose of14C-busulfan or busulfan (15 mg/kg). The distribution of busulfan to the brain was rapid and the ratio brain / plasma concentration was 0.74 during the time-course of busulfan. The elimination half-lives in plasma and brain were 3h for intact busulfan and 8h for the14C-radioactivity. The radioactivity remaining in plasma and brain after 24h was mostly busulfan metabolites e.g. sulfolane, 3-hydroxysulfolane and tetrahydrothiophene-1-oxide as identified by gas chromatography-mass spectrometry. The protein binding to rat plasma was low (9.2 +- 4.4%). © 1988 Springer-Verlag.