Biliary excretion of imatinib and its active metabolite CGP74588 during severe hepatic dysfunction

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...

Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...

The liver plays a pivotal role in eliminating drugs and their metabolites, primarily through a process known as biliary excretion. This process involves the hepatocytes, the primary cells in the liver that generate bile. A range of transporters actively expels polar drugs or hydrophilic drug metabolites into the bile, which transports the drugs and metabolites into the small intestine. From here, they are eventually expelled from the body through feces. In some instances, the original drug or a...