Severe hypoglycemia caused by a small dose of repaglinide and concurrent use of nilotinib and febuxostat in a patient with type 2 diabetes

Komatsu, Hitomi; Enomoto, Mariko; Shiraishi, Hisashi; Morita, Yasuyo; Hashimoto, Daisuke; Nakayama, Shuichi; Funakoshi, Shogo; Hirano, Seiki; Terada, Yoshio; Miyamura, Mitsuhiko; Fujimoto, Shimpei

doi:10.1007/s13340-020-00434-w

Cited by 2 publications

(1 citation statement)

References 22 publications

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“…Since the main scope of this review is to focus on discrepancies between published data and FDA and EMA guidelines, their results were not further explored here. Moreover, as OATP1B1 and OATP1B3 substrates used in the retrieved data have complex pharmacokinetic profiles involving drug-metabolizing enzymes and other transporters, the results of such case reports should be carefully analyzed to decide on the importance of each part of the pathway [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

Section: Effects Of Tkis On the Function Of Oatp1b1 And Oatp1b3mentioning

confidence: 99%

Role of OATP1B1 and OATP1B3 in Drug-Drug Interactions Mediated by Tyrosine Kinase Inhibitors

Garrison¹,

Talebi²,

Eisenmann³

et al. 2020

Pharmaceutics

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Failure to recognize important features of a drug’s pharmacokinetic characteristics is a key cause of inappropriate dose and schedule selection, and can lead to reduced efficacy and increased rate of adverse drug reactions requiring medical intervention. As oral chemotherapeutic agents, tyrosine kinase inhibitors (TKIs) are particularly prone to cause drug-drug interactions as many drugs in this class are known or suspected to potently inhibit the hepatic uptake transporters OATP1B1 and OATP1B3. In this article, we provide a comprehensive overview of the published literature and publicly-available regulatory documents in this rapidly emerging field. Our findings indicate that, while many TKIs can potentially inhibit the function of OATP1B1 and/or OATP1B3 and cause clinically-relevant drug-drug interactions, there are many inconsistencies between regulatory documents and the published literature. Potential explanations for these discrepant observations are provided in order to assist prescribing clinicians in designing safe and effective polypharmacy regimens, and to provide researchers with insights into refining experimental strategies to further predict and define the translational significance of TKI-mediated drug-drug interactions.

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Section: Effects Of Tkis On the Function Of Oatp1b1 And Oatp1b3mentioning

confidence: 99%

Role of OATP1B1 and OATP1B3 in Drug-Drug Interactions Mediated by Tyrosine Kinase Inhibitors

Garrison¹,

Talebi²,

Eisenmann³

et al. 2020

Pharmaceutics

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SLCO1B1 c.521T>C gene polymorphism decreases hypoglycemia risk in sulfonylurea-treated type 2 diabetic patients

Ragia

Atzemian

Maslarinou

et al. 2022

Drug Metabolism and Personalized Therapy

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Objectives Pharmacogenomics can explain some of the heterogeneity of sulfonylurea (SU)-related hypoglycemia risk. Recently, a role of OATP1B1, encoded by SLCO1B1 gene, on SU liver transport prior of metabolism has been uncovered. The aim of the present study was to explore the potential association of SLCO1B1 c.521T>C polymorphism, leading to reduced OATP1B1 function, with SU-related hypoglycemia risk. Methods Study cohort consists of 176 type 2 diabetes patients treated with the SUs glimepiride or gliclazide. 92 patients reported SU-related hypoglycemia, while 84 patients had never experienced a hypoglycemic event. Patients were previously genotyped for CYP2C9 *2 and *3 variant alleles that lead to decreased enzyme activity of the SU metabolizing enzyme CYP2C9 and have been associated with increased SU-related hypoglycemia risk. SLCO1B1 c.521T>C polymorphism was genotyped by use of PCR-RFLP analysis. Results SLCO1B1 c.521TC genotype frequency was significantly lower in hypoglycemic cases than non-hypoglycemic controls (15.2% vs. 32.1%, p=0.008). In an adjusted model, c.521TC genotype significantly reduced the risk of hypoglycemia (OR 0.371; 95% C.I. 0.167–0.822; p=0.015). In CYP2C9 intermediate metabolizers (n=54) c.521TC genotype frequency was significantly decreased in cases compared to controls (3 out of 36 cases, 8.3% vs. 7 out of 18 controls, 38.9%, p=0.012). A similar albeit not significant difference of SLCO1B1 c.521TC genotype was present in CYP2C9 extensive metabolizers (n=120) (18.2% in cases vs. 30.8% in controls, p=0.113). Conclusions We have found a protective effect of SLCO1B1 c.521C variant on SU-related hypoglycemia risk both independently and in interaction with CYP2C9 phenotypes. Our results suggest a possible linkage of SLCO1B1 c.521T>C polymorphism with variants in other genes impairing OATPs expressed in pancreatic islets that could interfere with SU tissue distribution.

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Severe hypoglycemia caused by a small dose of repaglinide and concurrent use of nilotinib and febuxostat in a patient with type 2 diabetes

Cited by 2 publications

References 22 publications

Role of OATP1B1 and OATP1B3 in Drug-Drug Interactions Mediated by Tyrosine Kinase Inhibitors

Role of OATP1B1 and OATP1B3 in Drug-Drug Interactions Mediated by Tyrosine Kinase Inhibitors

SLCO1B1 c.521T>C gene polymorphism decreases hypoglycemia risk in sulfonylurea-treated type 2 diabetic patients

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