Zohra Chadli, Ibtissem Hannachi, Nadia Ben Fredj, Hichem Loghmari, Haifa Ben Romdhane, Ahlem Slama, Amel Chaabane, Leila Safer, Karim Aouam
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引用次数: 0
Abstract
Introduction: Thiopurine drugs, the most commonly prescribed immunosuppressive agents used in the treatment of inflammatory bowel disease (IBD), are characterized by a narrow therapeutic window, which makes therapeutic drug monitoring (TDM) of thiopurine metabolites recommended. 6-thioguanine nucleotides (6-TGN) are considered the most active metabolites of the thiopurines and they are responsible for therapeutic efficacy and correlate with myelotoxicity. This present study aims to assess the usefulness of 6-TGN monitoring in Tunisian patients with IBD.
Patients and methods: We performed a retrospective study including patients with IBD treated by azathioprine and underwent a TDM of 6-TGN between May 2018 and December 2023. Samples of venous blood were collected at 2hours after medication intake. Concentrations values were determined, at the steady-state, using a technique of High-performance liquid chromatography (HPLC). Correlations between the 6-TGN concentrations and hematological parameters were assessed by Pearson's correlation coefficient.
Results: A total of 140 patients were included (65 men/75 women). The average concentration was 386.2±258.9pmol/8×108 RBCs. After an initial dose, only 49% of the patients had 6-TGN concentrations in the target range. The multiple TDM after AZA dose adjustment has shown improvement of the probability of obtaining 6-TGN concentration in the target range (69%). In our study, we demonstrated that 6-TGN concentrations were inversely correlated with hemoglobin levels, white cell, and neutrophil counts.
Conclusion: We have shown the usefulness of AZA TDM by determining the 6-TGN metabolite concentrations in Tunisian patients. However, this approach remains insufficient to optimize the treatment by azathioprine. Other approaches, such as genotyping patients for TPMT and NUD15 and adjusting AZA doses based on population pharmacokinetic models, appear to be essential for optimizing AZA therapy.
期刊介绍：
Thérapie is a peer-reviewed journal devoted to Clinical Pharmacology, Therapeutics, Pharmacokinetics, Pharmacovigilance, Addictovigilance, Social Pharmacology, Pharmacoepidemiology, Pharmacoeconomics and Evidence-Based-Medicine. Thérapie publishes in French or in English original articles, general reviews, letters to the editor reporting original findings, correspondence relating to articles or letters published in the Journal, short articles, editorials on up-to-date topics, Pharmacovigilance or Addictovigilance reports that follow the French "guidelines" concerning good practice in pharmacovigilance publications. The journal also publishes thematic issues on topical subject.
The journal is indexed in the main international data bases and notably in: Biosis Previews/Biological Abstracts, Embase/Excerpta Medica, Medline/Index Medicus, Science Citation Index.
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