Summary
The pharmacokinetics of high-dose busulphan was studied in adult patients with acute myeloblastic leukaemia after oral doses of 1 mg·kg−1 every 6 h for 4 days.
The mean steady-state plasma concentration was 1080 ng/ml−1 during the treatment. Individual steady-state concentrations after the last dose on average were 32% lower than those predicted from total AUC measurements following the first dose. Mean elimination half-life in plasma was 2.3 h after the last dose and 3.4 h after the first dose which suggests that busulfan may increase its own metabolic rate on repeated treatment.
The cerebrospinal fluid/plasma concentration ratio of busulphan was 1.3. Busulphan showed insignificant protein binding in plasma (7.4%). About 2% of the dose was excreted unchanged in the urine.
For the first time sulpholane, 3-hydroxysulpholane and tetrahydrothiophene 1-oxide were identified as urinary metabolites of busulphan in man.
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Hassan, M., Öberg, G., Ehrsson, H. et al. Pharmacokinetic and metabolic studies of high-dose busulphan in adults. Eur J Clin Pharmacol 36, 525–530 (1989). https://doi.org/10.1007/BF00558081
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DOI: https://doi.org/10.1007/BF00558081