Pharmacokinetic interactions between donafenib and empagliflozin or henagliflozin , lenvatinib and empagliflozin or henagliflozin in rats
Abstract
Abstract Donafenib(DONA) and lenvatinib(LEN) are small-molecule tyrosine kinase inhibitors(TKI) that are used to treat advanced hepatocellular carcinoma(HCC).Empagliflozin and henagliflozin are sodium-glucose cotransporter 2(T2DM) inhibitors that are used to treat type 2 diabetes(T2DM).Empagliflozin and henaglifiozin are uridine diphosphate glucuronosyltransferase(UGT)1A9, Substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)Donafenib is metabolized by UGT1A9 and is an inhibitor of UGT1A9 and lenvatinib is a substrate for P-gp and BCRP.T2DM is one of the risk factors for HCC progression, so the two drugs may be used in combination in clinical practice, but there is a lack of clear information about drug interactions. Therefore, the present study aimed to reveal the extent of drug interactions between donafenib, lenvatinib and empagliflozin and henagliflozin in rats and explore the possible mechanisms.Rats were divided into fourteen groups (n = 6) that received empaglifiozin(1,2),henagliflozin(3,4,)donafenib(5), lenvatinib(6), empaglifiozin and donafenib (7), hennagliflozin and donafenib (8), empaglifiozin and lenvatinib(9) ,henagliflozin and lenvatinib (10),donafenib and empaglifiozin (11), donafenib and henagliflozin (12),lenvatinib and empaglifiozin(13),lenvatinib and henagliflozin(14). The concentrations of drugs were determined by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The messenger RNA (mRNA)…
How strong is the evidence?
Evidence Hub reads this as a preprint, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 6 participants or records.
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