In vitro plasma protein binding of fenelidone

Finerenone (Finerenone), also known as BAY 94-8862 or Kerendia, is a nonsteroidal selective mineralocorticoid receptor antagonist. The drug is designed to block excessive activation of the mineralocorticoid receptor (MR), thereby mitigating its harmful effects. Mineralocorticoid receptors are expressed in tissues such as the kidney, heart, and blood vessels, and their overactivation is associated with a variety of disease states, especially in patients with diabetes, which may lead to the progression of chronic kidney disease and cardiovascular damage.

The pharmacological mechanism of fenelinone is that it can specifically bind to mineralocorticoid receptors, thereby preventing aldosterone and other mineralocorticoids from binding to the receptors, thereby inhibiting the expression of pro-inflammatory and pro-fibrotic genes induced by aldosterone. This effect is important for improving renal prognosis in patients with chronic kidney disease associated with type 2 diabetes.

In in vitro experiments, the plasma protein binding rate of fenelinone reached 92%, which is a very high value. Plasma protein binding rate refers to the percentage of a drug that binds to plasma proteins after it is absorbed into the blood. Under normal circumstances, drugs bind to plasma proteins at a certain ratio to form bound drugs and free drugs. Only free drugs have pharmaceutical activity, while conjugated drugs temporarily lose their pharmacological activity.

The high plasma protein binding of fenelidone means that it is primarily bound to plasma proteins in the blood, particularly to serum albumin. This combination contributes to the stable existence and distribution of the drug in the body, and may also affect the metabolism and excretion of the drug. However, since plasma protein binding is reversible, changes in plasma protein concentration may affect the free concentration of the drug and thus its efficacy.