Fat body mass and pharmacokinetics of oral 6-mercaptopurine in children with acute lymphoblastic leukemia.
To evaluate the reasons for the wide variability in bioavailability of orally administered 6-mercaptopurine in children with acute lymphoblastic leukemia, we studied several pharmacokinetic parameters of the drug in 18 affected children receiving remission maintenance therapy, and compared them with their anthropometric data and with the results of intestinal function tests. No correlation was found between estimates of small intestinal absorption (the oral lactose tolerance test and 1 h blood xylose test) and 6-mercaptopurine serum levels. Of the anthropometric measurements considered, only the weight/height percentile (an index of the fat body mass) strongly and linearly correlated with the area under the curve of 6-mercaptopurine. The dose of 75 mg of 6-mercaptopurine/m2 of body surface resulted in higher serum concentrations in children below the 75th percentile than in those with a weight/height ratio exceeding the 75th percentile. In conclusion, these data caution about the risk of underdosing 6-mercaptopurine in overweight children when administering it on the basis of body surface area.
Zuccaro
P
P
Department of Pediatrics, University of Naples, Italy.
Guandalini
S
S
Pacifici
R
R
Pichini
S
S
Di Martino
L
L
Guiducci
M
M
Giuliano
M
M
Di Tullio
M T
MT
Pettoello Mantovani
M
M
D000284:Administration, Oral; D000293:Adolescent; D001682:Biological Availability; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism
D015122:Mercaptopurine