Pharmacokinetic and metabolic studies of high-dose busulphan in adults.
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.
Hassan
M
M
Karolinska Pharmacy, Stockholm, Sweden.
Oberg
G
G
Ehrsson
H
H
Ehrnebo
M
M
Wallin
I
I
Smedmyr
B
B
Tötterman
T
T
Eksborg
S
S
Simonsson
B
B
D000328:Adult; D001711:Biotransformation; D002066:Busulfan / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D011485:Protein Binding
D002066:Busulfan