Inhibition of Human Thiopurine S-Methyltransferase by Various Nonsteroidal Anti-inflammatory Drugs in Vitro: A Mechanism for Possible Drug Interactions
| العنوان: | Inhibition of Human Thiopurine S-Methyltransferase by Various Nonsteroidal Anti-inflammatory Drugs in Vitro: A Mechanism for Possible Drug Interactions |
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| المؤلفون: | Kaili Anier, Kersti Oselin |
| المصدر: | Drug Metabolism and Disposition. 35:1452-1454 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Ketoprofen, Naproxen, Erythrocytes, Mefenamic acid, Allopurinol, Pharmaceutical Science, In Vitro Techniques, Pharmacology, Thiopurine S-Methyltransferase, Tolfenamic acid, medicine, Humans, Drug Interactions, Chromatography, High Pressure Liquid, Thiopurine methyltransferase, biology, Chemistry, Anti-Inflammatory Agents, Non-Steroidal, Methyltransferases, Drug interaction, Aminosalicylic Acids, Kinetics, Mechanism of action, Biochemistry, Data Interpretation, Statistical, biology.protein, Spectrophotometry, Ultraviolet, medicine.symptom, medicine.drug |
| الوصف: | Thiopurine S-methyltransferase (TPMT) is a biotransformation phase II enzyme responsible for the metabolic inactivation of thiopurine drugs. The present study was carried out to investigate the inhibitory potential of 15 nonsteroidal anti-inflammatory drugs (NSAIDs) on human TPMT activity in vitro. TPMT activity was measured in pooled human erythrocytes in the absence and presence of various NSAIDs using the previously published high-performance liquid chromatography-UV method. To determine the inhibition type and K(i) value for each compound, we performed kinetic analysis at five different inhibitor concentrations close to the IC(50) value obtained in preliminary experiments. Naproxen (K(i) = 52 microM), mefenamic acid (K(i) = 39 microM), and tolfenamic acid (K(i) = 50 microM) inhibited TPMT activity in a noncompetitive manner. The estimated K(i) values for the inhibition of TPMT by ketoprofen (K(i) = 172 microM) and ibuprofen (K(i) = 1043 microM) indicated that the propionic acid derivatives were relatively weak inhibitors of TPMT. Our results suggest that coadministration of thiopurines and various NSAIDs may lead to drug interactions. |
| تدمد: | 1521-009X 0090-9556 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::58e9627a96bd1052e8a3519a61046cd2Test https://doi.org/10.1124/dmd.107.016287Test |
| رقم الانضمام: | edsair.doi.dedup.....58e9627a96bd1052e8a3519a61046cd2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1521009X 00909556 |
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