PMID- 8531858
OWN - NLM
STAT- MEDLINE
DCOM- 19960130
LR  - 20171116
IS  - 0098-1532 (Print)
IS  - 0098-1532 (Linking)
VI  - 26
IP  - 2
DP  - 1996 Feb
TI  - Hepatotoxicity of 6-mercaptopurine in childhood acute lymphocytic leukemia: 
      pharmacokinetic characteristics.
PG  - 85-9
AB  - Treatment with 6-mercaptopurine (6MP) is associated with adverse gastrointestinal 
      (GI) and hepatic effects. Four patients, ages 6.9 +/- 2.6 (mean +/- S.D.) years, 
      with acute lymphocytic leukemia (ALL) on maintenance chemotherapy including 6MP, 
      developed nausea, vomiting, abdominal pain, elevated liver enzymes, and 
      hyperbilirubinemia after 1.4 +/- 1.0 (range 0.5-2) years. Liver biopsy in 1 
      patient was suggestive of drug-induced intrahepatic cholestatis. Symptoms 
      resolved and liver function returned to normal after discontinuation of 6MP. 
      Pharmacokinetic data of the symptomatic patients were compared with those of 25 
      ALL patients on the same protocol but without GI symptoms or hepatotoxicity. 
      Levels of 6-thioguanine nucleotides (6-TGN) and the methylated metabolites of 6MP 
      in red blood cells of the patients with hepatotoxicity, were not significantly 
      different when compared to patients without hepatotoxicity, suggesting similar 
      absorption of 6MP in both groups. Time to achieve peak 6MP levels was 
      significantly longer in the symptomatic patients compared to the asymptomatic 
      patients (P = 0.005). Peak levels and standardized concentration versus time 
      curve (AUC) per 1 mg of 6MP per m2 of body surface area were significantly lower 
      in the patients with hepatotoxicity (P = 0.016; P = 0.037, respectively). A 
      significant correlation between peak 6MP levels and standardized AUC (r = 0.729, 
      P < 0.0001) was found. These results suggest accumulation of 6MP and its 
      metabolites in the liver of the patients with GI symptoms, leading to 
      hepatotoxicity.
FAU - Berkovitch, M
AU  - Berkovitch M
AD  - Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 
      Toronto, Canada.
FAU - Matsui, D
AU  - Matsui D
FAU - Zipursky, A
AU  - Zipursky A
FAU - Blanchette, V S
AU  - Blanchette VS
FAU - Verjee, Z
AU  - Verjee Z
FAU - Giesbrecht, E
AU  - Giesbrecht E
FAU - Saunders, E F
AU  - Saunders EF
FAU - Evans, W E
AU  - Evans WE
FAU - Koren, G
AU  - Koren G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Med Pediatr Oncol
JT  - Medical and pediatric oncology
JID - 7506654
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - E7WED276I5 (Mercaptopurine)
SB  - IM
MH  - Antimetabolites, Antineoplastic/*adverse effects/pharmacokinetics/therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Cholestasis, Intrahepatic/chemically induced
MH  - Female
MH  - Humans
MH  - Liver/*drug effects/metabolism
MH  - Male
MH  - Mercaptopurine/*adverse effects/pharmacokinetics/therapeutic use
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/metabolism
EDAT- 1996/02/01 00:00
MHDA- 2000/06/20 09:00
CRDT- 1996/02/01 00:00
PHST- 1996/02/01 00:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1996/02/01 00:00 [entrez]
AID - 10.1002/(SICI)1096-911X(199602)26:2<85::AID-MPO3>3.0.CO;2-Q [pii]
AID - 10.1002/(SICI)1096-911X(199602)26:2<85::AID-MPO3>3.0.CO;2-Q [doi]
PST - ppublish
SO  - Med Pediatr Oncol. 1996 Feb;26(2):85-9. doi: 
      10.1002/(SICI)1096-911X(199602)26:2<85::AID-MPO3>3.0.CO;2-Q.