Related Experiment Video

Updated: Dec 29, 2025

Preparation of Naringenin Solution for In Vivo Application
08:18

Preparation of Naringenin Solution for In Vivo Application

Published on: August 10, 2021

3.7K

The oxidation and hypoglycaemic effect of sorafenib in streptozotocin-induced diabetic rats

Agnieszka Karbownik1, Anna Stachowiak2, Hanna Urjasz1

  • 1Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznan, Poland.

Pharmacological Reports : PR
|February 5, 2020
PubMed
Abstract

Insights

Diabetes significantly increases exposure to sorafenib and its metabolite in rats, suggesting altered drug metabolism. Sorafenib also caused hypoglycemia in diabetic rats, highlighting potential clinical implications for cancer patients with diabetes.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Oncology

Background:

  • Diabetes mellitus can impair the activity of cytochrome P450 3A4 (CYP3A4), an enzyme crucial for drug metabolism.
  • Sorafenib, a multi-targeted tyrosine kinase inhibitor (TKI), is metabolized by CYP3A4 and used to treat advanced cancers.

Purpose of the Study:

  • To compare the metabolic profile and exposure of sorafenib in healthy versus diabetic rats.
  • To investigate the impact of sorafenib on glucose levels in diabetic and healthy rats.

Main Methods:

  • Streptozotocin-induced diabetic rats and healthy control rats received a single oral dose of sorafenib (100 mg/kg).
  • Plasma concentrations of sorafenib and its N-oxide metabolite were quantified using validated high-performance liquid chromatography with ultraviolet detection.

Main Results:

  • Diabetic rats exhibited significantly higher plasma concentrations (Cmax) and area under the curve (AUC) for both sorafenib and its N-oxide metabolite compared to healthy rats.
  • Despite increased exposure, the ratios of N-oxide to sorafenib (AUC and Cmax) were similar between diabetic and healthy groups, suggesting unchanged oxidation pathways.
  • Sorafenib administration led to a significant reduction in blood glucose levels exclusively in the diabetic rat group.

Conclusions:

  • Diabetes significantly alters the pharmacokinetic exposure of sorafenib and its primary metabolite in rats.
  • The oxidation of sorafenib appears to be unaffected by diabetes, as indicated by consistent metabolite-to-drug ratios.
  • Sorafenib demonstrated a hypoglycemic effect in diabetic rats, warranting careful consideration in diabetic cancer patients undergoing treatment.
Keywords:
MetabolismSorafenibSorafenib-associated hypoglycaemiaStreptozotocin-induced diabetes

More Related Videos

Retinal Pathophysiological Evaluation in a Rat Model09:11

Retinal Pathophysiological Evaluation in a Rat Model

Published on: May 6, 2022

5.1K
Alternate Immersion in Glucose to Produce Prolonged Hyperglycemia in Zebrafish05:49

Alternate Immersion in Glucose to Produce Prolonged Hyperglycemia in Zebrafish

Published on: May 5, 2021

5.4K

Related Concept Videos

Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
536
Oral Hypoglycemic Agents: Sulfonylureas01:17

Oral Hypoglycemic Agents: Sulfonylureas

Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
674
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
475
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
514
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
497
Pathophysiology of Diabetes01:20

Pathophysiology of Diabetes

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
2.9K