Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide

Lysaa, Roy; Giverhaug, Trude; Wold, H. Libæk; Aarbakke, Jarle

doi:10.1007/s002280050038

Cited by 45 publications

(31 citation statements)

References 15 publications

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“…Finally, genotyping can reliably detect the major and rare variant at the human TPMT locus and may provide an explanation for TPMT deficiency [150]. Determination of the 3 most common alleles in Caucasians (*2, *3A, and *3C) identifies 90% to 96.2% of patients with altered enzyme activity [44,56,149] and may predict most AZA-induced toxicity.…”

Section: Genotyping Tpmt Vs Phenotyping Tpmtmentioning

confidence: 99%

Utility of Assessing Thiopurine S-methyltransferase Polymorphisms Before Azathioprine Therapy

Cabaleiro

Román²,

Gisbert³

et al. 2012

CDM

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Thiopurine S-methyltransferase (TPMT) catalyzes the methylation of thiopurine drugs, such as azathioprine and mercaptopurine, which are used in a variety of diseases. Several mutations in the TPMT gene correlate with low enzyme activity and subsequent adverse effects, mainly myelotoxicity. Hence, genotyping TPMT makes it possible to identify patients at high risk of drug toxicity and adjust dosage accordingly. However, further research about the availability of a reliable and universal screening method and more costeffectiveness studies are necessary.

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Section: Genotyping Tpmt Vs Phenotyping Tpmtmentioning

confidence: 99%

Utility of Assessing Thiopurine S-methyltransferase Polymorphisms Before Azathioprine Therapy

Cabaleiro

Román²,

Gisbert³

et al. 2012

CDM

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“…While leukopenia has been demonstated, 230 the severity of the interaction between these benzoic acid derivatives and azathioprine is not as well established as allopurinol. Furosemide has been shown in vivo to inhibit TPMT activity, 233 but its clinical relevance remains unknown. The prolonged use of trimethoprim-sulfamethoxazole in renal transplantation patients on azathioprine has been reported to cause neutropenia and thrombocytopenia.…”

Section: Drug Interactionsmentioning

confidence: 99%

Azathioprine in dermatology: The past, the present, and the future

Patel

Swerlick

McCall

2006

Journal of the American Academy of Dermatology

159

136

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“…65,78 In the patients receiving both thiopurines and mesalamine, adverse effects were observed more frequently. 78,79 TPMT activity may be inhibited also by therapeutic plasma levels of furosemide, thiazide diuretics, sulfasalazine, 5-acetylsalicylic acid, and nonsteroid antiinflammatory 67,80 Conversely, thiopurine therapy alone may increase activity of TPMT. 8,65,73 In some cases, monitoring of therapeutic 6-TGN blood concentrations may be as important as TPMT genotyping or phenotyping.…”

Section: Tpmt Polymorphismsmentioning

confidence: 94%

Advances of Molecular Clinical Pharmacology in Gastroenterology and Hepatology

Prandota¹

2010

American Journal of Therapeutics

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During developmental age, differences in pharmacodynamic reactions to several drugs may reflect polymorphisms of genes encoding drug-transporting proteins, receptors, drug targets, and gene products, whose disturbed activity sometimes plays an important role in certain diseases. Administration of drugs with a narrow therapeutic index may quite easily be associated with changes in pharmacokinetics and development of adverse drug reactions, which occasionally may cause fatalities. In such cases, polypragmasy and resulting drug interactions may enhance effects of changes in drug-metabolizing enzymes' activities. Phenotyping and genotyping of patients slowly are finding their place in some therapeutic regimens used in clinical gastroenterology and hepatology. At present, some assays to measure, for example, thiopurine S-methyltransferase activity are already commercially available. Polymorphisms of CYP450 enzymes, interleukins, and altered gene expression play an important role in some patients' various gastrointestinal tract and liver diseases. Herbal drugs also affect proinflammatory and antiinflammatory cytokine and nitric oxide balance in the body. Therapeutic use of recombined proteins, such as infliximab, natalizumab, onercept, humanized antibody to integrin α-4 β-7, or IFN-β in some large-bowel diseases increased therapeutic efficacy. IFN-α used in the patients with chronic hepatitis C improved cellular immunity in these subjects and exerted antiviral activity. Practical application of progress in pharmacogenetics, pharmacokinetics, pharmacodynamics, and use of bioproducts in novel therapeutic regimens has opened therapeutic frontiers and increased clinical safety.

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Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide

Abstract: Since S-methylation is a major pathway in the metabolism of thiopurines, our data point to the possibility of a clinically significant diuretic-thiopurine interaction in patients treated simultaneously with these drugs.

Cited by 45 publications

References 15 publications

Utility of Assessing Thiopurine S-methyltransferase Polymorphisms Before Azathioprine Therapy

Utility of Assessing Thiopurine S-methyltransferase Polymorphisms Before Azathioprine Therapy

Azathioprine in dermatology: The past, the present, and the future

Advances of Molecular Clinical Pharmacology in Gastroenterology and Hepatology

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