Thiopurines' Metabolites and Drug Toxicity: A Meta-Analysis

Journal of Clinical Medicine
Paula SousaFernando Magro

Abstract

Many questions remain unanswered regarding therapeutic drug monitoring (TDM) utility with thiopurines. This study aims to establish a relationship between thiopurines' metabolites and drug toxicity. We performed a systematic review with inclusion of studies evaluating the relationship between thiopurines' metabolites and drug toxicity. Meta-analysis of mean difference (MD), correlations and odds ratio (OR) was performed. We identified 21,240 records, 72 of which were eligible for meta-analysis. Levels of 6-thioguanine nucleotides (6-TGN) were higher in patients with leukopenia (MD 127.06 pmol/8 × 108 RBC) and gastrointestinal intolerance (MD 201.46 pmol/8 × 108 RBC), and lower in patients with hepatotoxicity (MD -40.6 pmol × 108 RBC). We established a significant correlation between 6-TGN and leukocytes (r = -0.21), neutrophils (r = -0.24) and alanine aminotransferase levels (r = -0.24). OR for leukopenia in patients with elevated 6-TGN was 4.63 (95%CI 2.24; 9.57). An optimal cut-off of 135 pmol/8 × 108 RBC for leukopenia was calculated (sensitivity 75.4%; specificity 46.4%). 6-methylmercaptopurine ribonucleotides (6-MMPR) were significantly associated with hepatotoxicity (MD 3241.2 pmol/8 × 108 RBC; OR 4.28; 95%CI 3.20; 5.71)....Continue Reading

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Citations

Aug 3, 2021·Frontiers in Medicine·Carla J Gargallo-PuyueloFernando Gomollón
Sep 5, 2021·Inflammatory Bowel Diseases·Nurulamin M NoorXavier Roblin
Sep 7, 2021·European Journal of Drug Metabolism and Pharmacokinetics·Ahmed B BayoumyNanne K H de Boer
Sep 26, 2021·Current Opinion in Pediatrics·Kristie N RamosKenneth S Ramos

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