The liver is an essential body organ involved in several physiological functions. One of these functions is the clearance and breakdown of certain drugs in the body into metabolites. Hence, liver disease can influence this process and can affect the metabolism of these drugs.
A clinical trial has been conducted to evaluate the safety of a drug known as tucatinib in patients with liver impairment.
Tucatinib is a medication used to treat breast cancer that has spread to other parts of the body. It works by blocking a protein called HER2, which promotes the growth of cancer cells. Tucatinib is predominantly cleared by the drug-metabolizing enzyme cytochrome P450 present in the liver.
Some people with breast cancer also have liver problems which can affect how their bodies process medications. Liver disease can result in reduced hepatic blood flow and drug-metabolizing enzyme activity, potentially causing alterations in drug distribution and decreased hepatic drug clearance. In addition, liver failure can affect the binding of drugs to plasma proteins, altering the levels of the free component of these drugs in the blood.
Clinical TrialTo help determine the safety and effectiveness of tucatinib in people with liver problems, a group of researchers conducted a clinical trial.
The trial involved giving tucatinib to a group of volunteers who had different levels of liver impairment. Overall, 37 volunteers were enrolled in the study: 15 volunteers with normal hepatic function, eight with mild hepatic impairment, eight with moderate hepatic impairment, and six with severe hepatic impairment. All participants were given a single oral dose of tucatinib 300 mg.
The researchers then monitored how the medication was absorbed, distributed, and eliminated from their bodies. They also looked at whether the medication caused any side effects or other problems.
ResultsThe results of the clinical trial showed that compared with healthy volunteers, tucatinib exposure was similar in volunteers with mild impairment and increased in those with moderate or severe impairment. These results emphasize that the tucatinib dose should be reduced from 300 mg to 200 mg in people with severe liver dysfunction while the traditional dose of 300 mg can be continued for healthy patients as well as patients with mild or moderate liver impairment.
Additionally, the researchers found that tucatinib was generally safe and well-tolerated by all of the volunteers, regardless of their level of liver impairment. Only 3 of the 37 participants developed minor side effects such as nausea, skin rash, and elevated liver enzyme levels.
The medication was absorbed and similarly eliminated from the body in all of the participants. This suggests that tucatinib may be a safe and effective treatment option for people with breast cancer and liver problems.
ConclusionOverall, the results of this clinical trial provide promising insights into the potential use of tucatinib in people with breast cancer and liver problems. They support the recommendation to reduce the dose of tucatinib from 300 mg twice daily to 200 mg twice daily in patients with severe impairment. As always, it's important to consult with your healthcare provider to determine the best treatment options for your individual needs and circumstances.
Clinical Pharmacokinetics, Dec-05-22