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

Authors

  • Ahmed Morales MD,

    1. Department of Medicine, University of Pennsylvania, Philadelphia, PA
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    • Dr. Lewis has received consulting honorarium and/or grant support from Centocor, Johnson and Johnson, Wyeth, Merck, GlaxoSmithKline, Elan, Takeda, Berlex, and Synta. Drs. Morales, Salguti, and Miao have no potential conflicts of interest to report.

  • Sandhya Salguti MD,

    1. Department of Medicine, Abington Memorial Hospital, Abington, PA
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    • Dr. Lewis has received consulting honorarium and/or grant support from Centocor, Johnson and Johnson, Wyeth, Merck, GlaxoSmithKline, Elan, Takeda, Berlex, and Synta. Drs. Morales, Salguti, and Miao have no potential conflicts of interest to report.

  • Chuan L. Miao MD,

    1. Department of Medicine, University of Pennsylvania, Philadelphia, PA
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    • Dr. Lewis has received consulting honorarium and/or grant support from Centocor, Johnson and Johnson, Wyeth, Merck, GlaxoSmithKline, Elan, Takeda, Berlex, and Synta. Drs. Morales, Salguti, and Miao have no potential conflicts of interest to report.

  • James D. Lewis MD, MSCE

    Corresponding author
    1. Department of Medicine, University of Pennsylvania, Philadelphia, PA
    2. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
    • Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 720 Blockley Hall, 423 Guardian Drive Philadelphia, PA 19104-6021
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    • Dr. Lewis has received consulting honorarium and/or grant support from Centocor, Johnson and Johnson, Wyeth, Merck, GlaxoSmithKline, Elan, Takeda, Berlex, and Synta. Drs. Morales, Salguti, and Miao have no potential conflicts of interest to report.


Abstract

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 × 108.

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 (ρ = 0.18, P = 0.04) and the dose in mg/kg (ρ = 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 (ρ = 0.24, P = 0.02). Compared with <1.0 mg/kg per day, doses of ≥1.5 mg/kg per day were strongly associated with 6-TGN levels of >230 pmol/8 × 108 RBC (adjusted odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.1–11.8). However, only 37% of patients receiving ≥1.0 mg/kg per day had 6-TGN levels of >230 pmol/8 × 108 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.

(Inflamm Bowel Dis 2006)

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