ISSN:
1432-1041
Keywords:
Key words Acute lymphoblastic leukaemia
;
6-Mercaptopurine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Objective: The pharmacokinetics of 6-mercaptopurine, including cerebrospinal-fluid (CSF) distribution, and the erythrocyte 6-thioguanine nucleotide concentrations were determined in children randomised to receive intravenous mercaptopurine for acute lymphoblastic leukaemia (ALL), according to the EORTC protocol ALL n°58881. Results: After 1 month of oral treatment at a dose of 50 mg · m−2 · day−1, the pharmacokinetic parameters were determined after the first i.v. administration of 1 g · m−2 (bolus dose of 0.2 g · m−2 followed by an 8-h infusion of 0.8 g · m−2) in 11 patients: systemic clearance was 23.02 l · h−1, volume of distribution was 0.75 l · kg−1, and elimination half-life was 1.64 h. The erythrocyte thioguanine concentrations were measured in the same 11 patients and increased significantly between the beginning and the end of infusion (10 pmol × 108 packed RBC) or within 24 h of infusion (223 pmol × 108 packed RBC). The CSF concentration was 3.78 μmol · l−1, 1–6 h after the beginning of infusion (n=28) and the CSF to plasma ratio was 0.15 (n=16). In patients receiving the oral dose of 50–165 mg · m−2 · day−1 of 6-mercaptopurine, CSF concentrations were below 0.18 μmol · l−1, 1–24 h after drug intake (n=67), and the CSF to plasma ratio was not calculated. Conclusion: Following the i.v. administration of 6-mercaptopurine, we observed high CSF concentrations of 6-mercaptopurine and an acute increase of erythrocyte thioguanine nucleotide concentrations. The clinical trial (EORTC protocol ALL n°5881), comparing the oral and i.v. administrations of mercaptopurine, will demonstrate if the i.v. administration reduces the incidence of CNS relapses.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050339
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