Abstract | PURPOSE: METHODS: A stepwise dose-escalation of allopurinol was performed in 11 azathioprine-pretreated IBD patients with inadequately low 6-TGN concentrations (<235 pmol/8 × 10(8) erythrocytes) and/or elevated MMPN concentrations (>5,000 pmol/8 × 10(8) erythrocytes) and/or elevated liver enzymes ( alanine aminotransferase and/or aspartate aminotransferase levels one- to threefold the upper limit of normal). Six patients were recruited into an open study, and five were treated in the context of an individualized therapeutic approach. Adverse effects, azathioprine metabolites, liver enzymes and whole blood counts were monitored two to three times per month. RESULTS: Adequate 6-TGN concentrations were achieved with a combination of 25 mg allopurinol and 50 mg azathioprine in one patient and with 50 mg allopurinol and 50 mg azathioprine in nine patients. Median 6-TGN concentrations (range) were 336 (290-488) pmol/8 × 10(8) erythrocytes after an 8-week-long intake of the final dose combination. One patient dropped out due to nausea after the first intake. MMPN concentrations and liver enzymes normalized immediately in all affected patients. All patients finishing the dose-escalation regimen tolerated the treatment without toxicity. CONCLUSIONS:
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Authors | Ivanka Curkovic, Katharina M Rentsch, Pascal Frei, Michael Fried, Gerhard Rogler, Gerd A Kullak-Ublick, Alexander Jetter |
Journal | European journal of clinical pharmacology
(Eur J Clin Pharmacol)
Vol. 69
Issue 8
Pg. 1521-31
(Aug 2013)
ISSN: 1432-1041 [Electronic] Germany |
PMID | 23588559
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Guanine Nucleotides
- Thionucleotides
- 6-thioguanylic acid
- Allopurinol
- 6-methylthiopurine
- Mercaptopurine
- Azathioprine
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Topics |
- Adult
- Aged
- Allopurinol
(administration & dosage)
- Azathioprine
(administration & dosage)
- Female
- Guanine Nucleotides
(metabolism)
- Humans
- Inflammatory Bowel Diseases
(drug therapy)
- Male
- Mercaptopurine
(analogs & derivatives, metabolism)
- Middle Aged
- Thionucleotides
(metabolism)
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