PMID- 18031107
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121002
LR  - 20181025
IS  - 1173-8804 (Print)
IS  - 1173-8804 (Linking)
VI  - 8
IP  - 6
DP  - 1997 Dec
TI  - Optimisation of azathioprine immunosuppression after organ transplantation by 
      pharmacological measurements.
PG  - 446-56
AB  - Azathioprine undergoes extensive metabolism in vivo. Most of its 
      immunosuppressive and myelotoxic effects are exerted by the intracellular 
      metabolites 6-thioguanine nucleotides (6-TGN). There is large individual 
      variability in thiopurine pharmacokinetics. When transplant recipients are 
      started on the standard azathioprine dosage, low and probably subtherapeutic 
      6-TGN concentrations [<100 pmol/8 x 10(8) red blood cells (RBC)] are measured in 
      the majority of patients with normal kidney function. When renal function is 
      severely impaired, 6-TGN concentrations rise 8- to 10-fold or higher. Due to 
      genetic polymorphism, the activity of the enzyme thiopurine methyltransferase 
      (TPMT) is intermediate to undetectable in approximately 11% of the population. 
      With low TPMT activity, transmethylation is reduced and more intermediate 
      metabolites are left for alternative pathways such as 6-TGN formation. High 6-TGN 
      concentrations are associated with increased frequency and severity of 
      leucopenia. It has been suggested that active monitoring of azathioprine to keep 
      6-TGN concentrations between 100 and 200 pmol/8 x 10(8) RBC may contribute to 
      more effective treatment by reducing the incidence of rejection episodes and 
      leucopenia. Such monitoring is currently being evaluated in a controlled, 
      prospective study of renal allograft recipients.
FAU - Bergan, S
AU  - Bergan S
AD  - Institute of Clinical Biochemistry and Department of Clinical Pharmacology, 
      National Hospital, University of Oslo, Norway.
LA  - eng
PT  - Journal Article
PL  - New Zealand
TA  - BioDrugs
JT  - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
JID - 9705305
EDAT- 2007/11/23 09:00
MHDA- 2007/11/23 09:01
CRDT- 2007/11/23 09:00
PHST- 2007/11/23 09:00 [pubmed]
PHST- 2007/11/23 09:01 [medline]
PHST- 2007/11/23 09:00 [entrez]
AID - 080604 [pii]
AID - 10.2165/00063030-199708060-00005 [doi]
PST - ppublish
SO  - BioDrugs. 1997 Dec;8(6):446-56. doi: 10.2165/00063030-199708060-00005.