脑脊液介导的大脑清除:来自人类研究的见解

Cerebrospinal fluid (CSF) is a colorless liquid that flows around the brain and the spinal cord, playing a vital role in the protection, support, and overall function of the central nervous system (CNS). CSF production, circulation, and absorption are tightly regulated processes essential for the brain and spinal cord to function properly.
CSF Production
CSF is produced mainly in the choroid plexus, a network of capillaries and ependymal cells located within the ventricular system of the brain....

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...

Hepatic clearance refers to the volume of blood cleared of a drug by the liver per unit of time. It plays a crucial role in drug metabolism and elimination. While hepatic clearance is commonly estimated by subtracting renal clearance from total body clearance, other pathways, such as pulmonary or biliary clearance, may also contribute. However, these pathways are generally less significant than hepatic and renal clearance.
Most drugs undergo restrictive clearance, which is proportional to the...

The glomerular filtration rate (GFR) is a critical marker of kidney function, reflecting the efficiency of filtration by the glomeruli. Renal clearance of specific substances, such as inulin or creatinine, is commonly used to measure GFR.
Renal clearance refers to the volume of plasma cleared of a specific substance, such as creatinine, per unit of time. To measure clearance, urine samples are collected over a 24-hour period during each bladder voiding, followed by a single blood sample at the...

Drug elimination refers to drug removal from the body, either through urine or bile, by the kidneys or liver, respectively. A pharmacokinetic parameter, drug clearance, measures the efficiency of drug removal from the bloodstream within a specific time frame. It is calculated as the rate at which a drug is eliminated from plasma divided by the drug's concentration in plasma.
Drug clearance is not limited to renal excretion but encompasses all organs involved in drug elimination, including...

The fluid mosaic model was first proposed as a visual representation of research observations. The model comprises the composition and dynamics of membranes and serves as a foundation for future membrane-related studies. The model depicts the structure of the plasma membrane with a variety of components, which include phospholipids, proteins, and carbohydrates. These integral molecules are loosely bound, defining the cell’s border and providing fluidity for optimal function.