PMID- 11344381
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20191104
IS  - 1075-2765 (Print)
IS  - 1075-2765 (Linking)
VI  - 8
IP  - 3
DP  - 2001 May-Jun
TI  - High 6-thioguanine nucleotide levels and low thiopurine methyltransferase 
      activity in patients with lupus erythematosus treated with azathioprine.
PG  - 147-50
AB  - Azathioprine (AZA) is characterized by a high interindividual variability in 
      bioavailability and metabolism. AZA is converted into 6-thioguanine nucleotides 
      (6-TGN) to which the immune modifier activity is attributed. The 6-TGN levels are 
      known to be affected by the activity of the key enzyme, thiopurine 
      methyltransferase (TPMT), which is under genetic dependence. The authors measured 
      a significantly lower TPMT activity in 53 women with systemic lupus erythematosus 
      (SLE) (12.2 +/- 2.4 pmol/h/ml RBC; P < 0.01) when compared with 30 healthy 
      control participants (13.15 +/- 3.1 pmol/h/ml RBC) but not with 28 patients with 
      other dysimmune diseases (non-SLE; 13.0 +/- 3.0 pmol/h/ml RBC; P = 0.10). To 
      evaluate the impact of TPMT activity on the concentrations of AZA metabolites, we 
      measured the TPMT activity and 6-TGN levels in a subgroup of 26 patients in 
      remission and treated with a stable dose of AZA (mean value: 1.9 +/- 0.5 
      mg/kg/day) for at least six months (n = 13 with SLE and n = 13 with other 
      dysimmune diseases, ie, non-SLE). In such a subgroup, no correlation between 
      6-TGN levels and TPMT activity was observed. However, patients with SLE presented 
      lower TPMT activity and higher 6-TGN levels (215 +/- 123 versus 140 +/- 75 pmol/8 
      x 10(8) RBC in non-SLE patients; P < 0.04). It must be noted that transient 
      increase in 6-methylmercaptopurine levels (6-MMP), a putative toxic metabolite 
      (up to 21.7 nmol/8 x 10(8) RBC), was more frequently observed in the non-SLE 
      group (P < 0.01). Even if a relationship was observed between low TPMT activity 
      and 6-TGN levels in SLE, its clinical impact appears to be limited as far as 
      regular hematologic controls are performed.
FAU - Decaux, G
AU  - Decaux G
AD  - General Internal Medicine Department, University Hospital Erasme, Brussels, 
      Belgium. guy.decaux@skynet.be
FAU - Horsmans, Y
AU  - Horsmans Y
FAU - Houssiau, F
AU  - Houssiau F
FAU - Desager, J P
AU  - Desager JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Ther
JT  - American journal of therapeutics
JID - 9441347
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.67 (thiopurine methyltransferase)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Azathioprine/therapeutic use
MH  - Female
MH  - Guanine Nucleotides/*metabolism
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Lupus Erythematosus, Systemic/drug therapy/*metabolism
MH  - Methyltransferases/*metabolism
MH  - Thionucleotides/*metabolism
EDAT- 2001/05/10 10:00
MHDA- 2001/07/20 10:01
CRDT- 2001/05/10 10:00
PHST- 2001/05/10 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/05/10 10:00 [entrez]
AID - 10.1097/00045391-200105000-00002 [doi]
PST - ppublish
SO  - Am J Ther. 2001 May-Jun;8(3):147-50. doi: 10.1097/00045391-200105000-00002.