Relationship between 6-mercaptopurine dose and 6-Thioguanine nucleotide levels in patients with inflammatory bowel disease

✍ Scribed by Ahmed Morales; Sandhya Salguti; Chuan L. Miao; James D. Lewis

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 108 KB
• Volume: 13
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20028

✦ Synopsis

Background:

6-thioguanine nucleotides (6-tgn) are active metabolites of azathioprine (aza) and 6-mercaptopurine (6mp). higher remission rates have been observed in patients with higher 6-tgn levels. however, many physicians prescribe aza/6mp using milligrams per kilogram (mg/kg) dosing regimens without measuring 6-tgn levels. the aim of this study was to examine the association between 6mp dose and 6-tgn levels.

Methods:

We conducted a cross-sectional study of patients treated for inflammatory bowel disease (ibd) with aza or 6mp, whose 6-tgn levels were measured. patients with low or intermediate thiopurine methyl transferase (tpmt) activity were excluded. aza dose was converted to 6mp equivalents. the relationship between dose and 6-tgn levels was assessed with the spearman correlation coefficient. we used logistic regression to assess the relationship between dose and 6-tgn levels of >230 pmol/8 x 10(8).

Results:

In this study, 155 patients met our inclusion criteria (median dose, 1.01 +/- 0.40; range, 0.61-1.41 mg/kg). there was a weak correlation between 6-tgn levels and the absolute dose (rho = 0.18, p = 0.04) and the dose in mg/kg (rho = 0.19, p = 0.03). the correlation between mg/kg dosage and 6-tgn levels was slightly stronger in those using concomitant 5-aminosalicylate (5-asa) medications (rho = 0.24, p = 0.02). compared with <1.0 mg/kg per day, doses of > or =1.5 mg/kg per day were strongly associated with 6-tgn levels of >230 pmol/8 x 10(8) rbc (adjusted odds ratio [or] = 3.7, 95% confidence interval [ci] = 1.1-11.8). however, only 37% of patients receiving > or =1.0 mg/kg per day had 6-tgn levels of >230 pmol/8 x 10(8) rbc.

Conclusions:

6mp dose is weakly associated with 6-tgn levels. the use of standard mg/kg dosing regimens will result in low 6-tgn levels in most patients.