The course of biological parameters and 6-mercaptopurine pharmacokinetics during maintenance treatment of children with acute lymphoblastic leukaemia.
Twenty patients on maintenance therapy (MT) for acute lymphoblastic leukaemia (ALL) with oral 6-mercaptopurine (6-MP) and methotrexate (MTX) were studied. White cell and red cell indices and platelets counts were monitored every second week as were drug levels. Mean values for 6-MP and MTX doses, and blood component parameters were calculated for each 6-month period for the whole patient group. 6-MP plasma concentrations and liver-function tests were determined once every six months and mean values calculated. 6-MP and MTX mean doses did not change significantly during MT. The mean area under the concentration versus time curve (AUC) 0-4 hours varied slightly from the start to the end of the MT (257 and 296 ng/ml.h, respectively). The mean plasma peak concentration increased from 98 ng/ml to 195 ng/ml (p less than 0.01) during the same period. There were significant decreases between the initial white blood cell counts (WBC) and red blood cell counts (RBC) as compared to levels at the end of therapy (p less than 0.01 and 0.02, respectively). A linear correlation was found between 6-MP peak concentrations and both WBC (r = 0.96) and RBC (r = 0.87). At the end of MT liver function tests became normal in all except 6 patients. In conclusion, MT have moderate effects on bone marrow and liver and monitoring 6-MP plasma concentration might be of value for determination of the optimal WBC levels during MT.
Hayder
S
S
Department of Paediatrics, Karolinska Hospital, Stockholm, Sweden.
Björk
O
O
Lafolie
P
P
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D015122:Mercaptopurine / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D008727:Methotrexate / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D015122:Mercaptopurine; D008727:Methotrexate