PMID- 9357091
OWN - NLM
STAT- MEDLINE
DCOM- 19971217
LR  - 20190905
IS  - 0163-4356 (Print)
IS  - 0163-4356 (Linking)
VI  - 19
IP  - 5
DP  - 1997 Oct
TI  - Patterns of azathioprine metabolites in neutrophils, lymphocytes, reticulocytes, 
      and erythrocytes: relevance to toxicity and monitoring in recipients of renal 
      allografts.
PG  - 502-9
AB  - Monitoring of azathioprine (AZA) therapy by the measurement of 6-thioguanine 
      nucleotides (6-TGN) concentrations in red blood cells (RBC) may improve safety 
      and ensure optimal immunosuppressive effects of AZA in organ transplantation. The 
      authors explored the rationale for such monitoring by measuring thiopurine 
      metabolites in peripheral blood cell types that are more relevant to the effects 
      and kinetics of AZA and its active metabolites. Neutrophil granulocytes were 
      isolated by density gradient centrifugation, and CD4+ lymphocytes and 
      reticulocytes by using specific immunomagnetic beads. In neutrophils, 6-TGN 
      concentrations had median measurements 31 times higher than in RBCs. In contrast 
      to the high methylated mercaptopurine (me-MP) concentrations in RBCs, these 
      metabolites were not detected in the neutrophils. Thiopurine metabolite levels 
      were lower than the analytic limit of detection in all the CD4+ samples. The 
      concentrations of 6-TGN and me-MPs were lower in reticulocytes than in RBCs in 
      general, indicating that thiopurine metabolites are taken up by RBCs in the 
      circulation. This study's findings, that 6-TGN concentrations are very high in 
      neutrophils, whereas me-MPs are undetectable, many explain the specific 
      neutropenic adverse effect of AZA. The results also add support to monitoring AZA 
      through measurements of 6-TGN and me-MPs in RBCs.
FAU - Bergan, S
AU  - Bergan S
AD  - Institute of Clinical Biochemistry, National Hospital, University of Oslo, 
      Norway.
FAU - Bentdal, O
AU  - Bentdal O
FAU - Sodal, G
AU  - Sodal G
FAU - Brun, A
AU  - Brun A
FAU - Rugstad, H E
AU  - Rugstad HE
FAU - Stokke, O
AU  - Stokke O
LA  - eng
PT  - Case Reports
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ther Drug Monit
JT  - Therapeutic drug monitoring
JID - 7909660
RN  - 0 (Immunosuppressive Agents)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Aged
MH  - Azathioprine/*blood
MH  - Drug Monitoring
MH  - Erythrocytes/*metabolism
MH  - Humans
MH  - Immunosuppressive Agents/*blood
MH  - Kidney Failure, Chronic/blood/therapy
MH  - Kidney Transplantation/*physiology
MH  - Lymphocytes/*metabolism
MH  - Male
MH  - Neutrophils/*metabolism
MH  - Reticulocytes/*metabolism
EDAT- 1997/11/14 00:00
MHDA- 1997/11/14 00:01
CRDT- 1997/11/14 00:00
PHST- 1997/11/14 00:00 [pubmed]
PHST- 1997/11/14 00:01 [medline]
PHST- 1997/11/14 00:00 [entrez]
AID - 10.1097/00007691-199710000-00003 [doi]
PST - ppublish
SO  - Ther Drug Monit. 1997 Oct;19(5):502-9. doi: 10.1097/00007691-199710000-00003.