Hypoglycemia possibly caused by CYP2C9-mediated drug interaction in combination with bucolome: a case report

Tateishi, Hiroki; Miyazu, Daisuke; Kurinami, Miho; Ieiri, Ichiro; Hirakawa, Masakazu; Watanabe, Hiroyuki

doi:10.1186/s40780-021-00221-y

Cited by 2 publications

(1 citation statement)

References 21 publications

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“…For example, Tateishi and coworkers reported the risk of hypoglycemia prompted by the combination of bucolome and glimepiride. Such hypoglycemia may be caused by CYP2C9-mediated drug interactions in combination with bucolome ( Tateishi et al, 2021 ). Therefore, determining the potential for CYPs inhibition can help weed out underperforming drug candidates in the early drug discovery process to reduce the occurrence of termination of drug development programs, drug withdrawal from the market, or restriction of therapeutic use, which is crucial for drug discovery and development.…”

Section: Introductionmentioning

confidence: 99%

DEEPCYPs: A deep learning platform for enhanced cytochrome P450 activity prediction

Cai

Wei

et al. 2023

Front. Pharmacol.

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Cytochrome P450 (CYP) is a superfamily of heme-containing oxidizing enzymes involved in the metabolism of a wide range of medicines, xenobiotics, and endogenous compounds. Five of the CYPs (1A2, 2C9, 2C19, 2D6, and 3A4) are responsible for metabolizing the vast majority of approved drugs. Adverse drug-drug interactions, many of which are mediated by CYPs, are one of the important causes for the premature termination of drug development and drug withdrawal from the market. In this work, we reported in silicon classification models to predict the inhibitory activity of molecules against these five CYP isoforms using our recently developed FP-GNN deep learning method. The evaluation results showed that, to the best of our knowledge, the multi-task FP-GNN model achieved the best predictive performance with the highest average AUC (0.905), F1 (0.779), BA (0.819), and MCC (0.647) values for the test sets, even compared to advanced machine learning, deep learning, and existing models. Y-scrambling testing confirmed that the results of the multi-task FP-GNN model were not attributed to chance correlation. Furthermore, the interpretability of the multi-task FP-GNN model enables the discovery of critical structural fragments associated with CYPs inhibition. Finally, an online webserver called DEEPCYPs and its local version software were created based on the optimal multi-task FP-GNN model to detect whether compounds bear potential inhibitory activity against CYPs, thereby promoting the prediction of drug-drug interactions in clinical practice and could be used to rule out inappropriate compounds in the early stages of drug discovery and/or identify new CYPs inhibitors.

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Section: Introductionmentioning

confidence: 99%

DEEPCYPs: A deep learning platform for enhanced cytochrome P450 activity prediction

Cai

Wei

et al. 2023

Front. Pharmacol.

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Antihyperglycaemics/bucolome/warfarin

2021

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Antihyperglycaemics/bucolome/warfarinHypoglycaemia and drug-drug interactions: case report An 81-year-old woman developed hypoglycaemia during concomitant administration of bucolome, glimepiride and warfarin. Additionally, hypoglycaemia was attributed to voglibose [routes not stated; not all times to reactions onsets stated].The woman, who had hypertension and type 2 diabetes, had been receiving glimepiride 2 mg/day (twice daily, after breakfast and dinner), voglibose 0.6 mg/day (three times daily, just before meals), amlodipine and telmisartan, with good compliance for >6 months. She was admitted to hospital in Japan because of exertional dyspnea. Aortic stenosis was diagnosed, and she underwent an elective aortic valve replacement (day 0). On postoperative day 1, meals were started in the evening. On the same day, she started receiving ultra-rapid-acting insulin therapy. Voglibose and glimepiride, which had been discontinued for surgery, were resumed on postoperative day 2. Also, she started receiving warfarin [warfarin potassium] 2 mg/day to prevent thromboembolism, and the dose of warfarin was further adjusted using the prothrombin time-INR. Due to low PT-INR on postoperative day 9, she started receiving bucolome 300 mg/day to enhance the effect of warfarin. Other post-surgery medications included carbocisteine [L-Carbocisteine], magnesium-oxide, sodium ferrous citrate, furosemide and heparin [heparin sodium]. Subsequently, PT-INR started to rise after the initiation of bucolome; however, a decrease in blood glucose level was noted from day 2 of bucolome therapy. On day 6 of bucolome therapy, she experienced hypoglycaemia (56-57 mg/dL) before lunch and dinner. A possibility of drug-induced hypoglycaemia due to bucolome was suspected.Therefore, voglibose was stopped on the following day. Subsequently, increase in blood glucose levels was noted before lunch and dinner and at bedtime. However, the blood glucose levels before breakfast were unchanged (70-90 mg/dL). Thereafter, the woman was moved to another hospital since hypoglycaemia (<70 mg/dL) was not observed, and she was stable (day 19). A special diet (for diabetes) was provided to her during hospital stay. Apart from meals, she received maintenance fluid through peripheral vessels from postoperative day 1 to day 15. It was noted that she developed hypoglycaemia secondary to voglibose and multiple drug-drug interactions. Inhibition of CYP2C9, which influences the effect of warfarin, by bucolome caused an increase in the blood concentration of warfarin, and warfarin enhanced the hypoglycaemic effect of glimepiride by inhibiting its metabolism via CYP2C9. Eventually, drug interaction, caused by inhibition of CYP2C9 by bucolome and competitive inhibition of CYP2C9 by warfarin, affected the pharmacokinetics of glimepiride.

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Hypoglycemia possibly caused by CYP2C9-mediated drug interaction in combination with bucolome: a case report

Cited by 2 publications

References 21 publications

DEEPCYPs: A deep learning platform for enhanced cytochrome P450 activity prediction

DEEPCYPs: A deep learning platform for enhanced cytochrome P450 activity prediction

Antihyperglycaemics/bucolome/warfarin

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