PMID- 10217345
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20190905
IS  - 0163-4356 (Print)
IS  - 0163-4356 (Linking)
VI  - 21
IP  - 2
DP  - 1999 Apr
TI  - Determination of 6-thioguanine and 6-methylmercaptopurine metabolites in renal 
      transplantation recipients and patients with glomerulonephritis treated with 
      azathioprine.
PG  - 231-7
AB  - The metabolism of azathioprine (AZA) was studied by monitoring the concentrations 
      of red blood cell (RBC) 6-thioguanine nucleotides (6-TGN) and of 
      6-methylmercaptopurine metabolites (6-mMP) in 27 renal transplantation recipients 
      and in 10 patient subjects with glomerulonephritis (GN). Concentrations of 6-TGNs 
      and 6-mMP metabolites were measured using high-performance liquid chromatography 
      (HPLC). Six patients from the group of renal transplantation recipients were also 
      administered allopurinol. Median values of RBC 6-TGN and of 6-mMP metabolites 
      concentrations in 21 renal transplantation recipients (without allopurinol) were 
      122 pmol/8x10(8) RBCs (range, <60-298) and 280 pmol/8x10(8) RBC (range, 
      <150-1330), respectively; there was no correlation between concentrations of 
      6-TGN and of 6-mMP metabolites. The group of 21 renal transplantation recipients 
      received different AZA doses (100 or 50 mg/d) related to clinical symptoms of AZA 
      intolerance. The median values of 6-TGN concentrations in these subgroups were 
      131 and 122 pmol/8x10(8) RBCs and were not significantly different. Median values 
      of 6-TGN concentrations in patients given allopurinol were significantly higher, 
      despite AZA dose reduction, compared with the group without allopurinol and were 
      equal to 363 and 122 pmol/8x10(8) RBC, p < 0.004, respectively. No significant 
      differences were found between the concentrations of 6-mMP metabolites in either 
      group. In the group of renal transplantation recipients, a significant 
      correlation between white blood cell (WBC) count and 6-TGN concentration was 
      established (r(s) = -0.59, p < 0.005). In the group of GN patients, the median 
      values of 6-TGN and of 6-mMP metabolites concentrations were 108 pmol/8x10(8) 
      RBCs (range, 0-297) and 420 pmol/8x10(8) RBC (range, 0-1440), respectively. There 
      were no significant correlations between either the WBC count and 6-TGN 
      concentrations or between 6-TGN concentrations and 6-mMP metabolites. We expect 
      the results of our study to provide indications for better individualization of 
      AZA therapy.
FAU - Chrzanowska, M
AU  - Chrzanowska M
AD  - Department of Physical Chemistry, Karol Marcinkowski University of Medical 
      Sciences, Poznan, Poland.
FAU - Krzymanski, M
AU  - Krzymanski M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ther Drug Monit
JT  - Therapeutic drug monitoring
JID - 7909660
RN  - 0 (Antimetabolites)
RN  - 0 (Immunosuppressive Agents)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adult
MH  - Allopurinol/blood/pharmacokinetics
MH  - Antimetabolites/blood/pharmacokinetics
MH  - Azathioprine/administration & dosage/blood/*pharmacokinetics
MH  - Erythrocytes/metabolism
MH  - Female
MH  - Glomerulonephritis/*blood/drug therapy
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/blood/*pharmacokinetics
MH  - *Kidney Transplantation
MH  - Male
MH  - Mercaptopurine/*analogs & derivatives/metabolism
MH  - Middle Aged
MH  - Thioguanine/*metabolism
EDAT- 1999/04/27 00:00
MHDA- 1999/04/27 00:01
CRDT- 1999/04/27 00:00
PHST- 1999/04/27 00:00 [pubmed]
PHST- 1999/04/27 00:01 [medline]
PHST- 1999/04/27 00:00 [entrez]
AID - 10.1097/00007691-199904000-00015 [doi]
PST - ppublish
SO  - Ther Drug Monit. 1999 Apr;21(2):231-7. doi: 10.1097/00007691-199904000-00015.