On the limitation of 6-tioguaninenucleotide monitoring during tioguanine treatment

Aliment Pharmacol Ther. 2005 Sep 1;22(5):447-51. doi: 10.1111/j.1365-2036.2005.02581.x.

Abstract

Background: Tioguanine (thioguanine) has been proposed as a rescue thiopurine for azathioprine or mercaptopurine intolerant inflammatory bowel disease patients. The use of tioguanine leads to high 6-tioguaninenucleotide (6-thioguaninenucleotide) levels in red blood cells but, contra-intuitively, these have yet not been associated with an increased risk of myelotoxicity.

Aim: To assess the role of 6-tioguaninenucleotide concentrations in developing myelotoxicity during tioguanine treatment.

Methods: Database analysis of 25 patients treated with tioguanine. Clinical findings and laboratory parameters were related to 6-tioguaninenucleotide levels.

Results: One patient developed a myelodepression (21 mg TG/day for 3 months and 6-tioguaninenucleotide 714 pmol/8 x 10(8) red blood cells). 6-Tioguaninenucleotide levels varied greatly between individuals (mean 6-tioguaninenucleotide level 621 pmol/8 x 10(8) red blood cells, s.d. 340 pmol/8 x 10(8) red blood cells and range 34-1653 pmol/8 x 10(8) red blood cells). The TG dosages (mean 20.6 mg/day and median 20 mg/day) did not correlate with 6-tioguaninenucleotide levels (r = 0.31, N.S.). High 6-tioguaninenucleotide levels (>450 pmol/8 x 10(8) red blood cells) did not effect haemoglobin concentrations (mean 8 mmol/L), peripheral leucocyte (mean 7.5 x 10(9)/L) or platelet counts (mean 298 x 10(9)/L). No correlations were established between laboratory parameters, type of disease and 6-tioguaninenucleotide level.

Conclusion: High 6-tioguaninenucleotide levels in erythrocytes (>450 pmol/8 x 10(8)) during TG treatment compared to azathioprine or mercaptopurine treatment are not indicative for (developing) myelotoxicity.

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Bone Marrow Diseases / chemically induced
  • Bone Marrow Diseases / prevention & control
  • Celiac Disease / drug therapy*
  • Celiac Disease / metabolism
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism
  • Crohn Disease / drug therapy*
  • Crohn Disease / metabolism
  • Female
  • Hepatitis, Autoimmune / drug therapy*
  • Hepatitis, Autoimmune / metabolism
  • Humans
  • Male
  • Thioguanine / adverse effects
  • Thioguanine / metabolism
  • Thioguanine / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Thioguanine