Biological half-life | EPFL Graph Search

Are you an EPFL student looking for a semester project?

Work with us on data science and visualisation projects, and deploy your project as an app on top of GraphSearch.

Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma. It is denoted by the abbreviation . This is used to measure the removal of things such as metabolites, drugs, and signalling molecules from the body. Typically, the biological half-life refers to the body's natural detoxification (cleansing) through liver metabolism and through the excretion of the measured substance through the kidneys and intestines. This concept is used when the rate of removal is roughly exponential. In a medical context, half-life explicitly describes the time it takes for the blood plasma concentration of a substance to halve (plasma half-life) its steady-state when circulating in the full blood of an organism. This measurement is useful in medicine, pharmacology and pharmacokinetics because it helps determine how much of a drug needs to be taken and how frequently it needs to be taken if a certain average amount is needed constantly. By contrast, the stability of a substance in plasma is described as plasma stability. This is essential to ensure accurate analysis of drugs in plasma and for drug discovery. The relationship between the biological and plasma half-lives of a substance can be complex depending on the substance in question, due to factors including accumulation in tissues, protein binding, active metabolites, and receptor interactions. The biological half-life of water in a human is about 7 to 14 days. It can be altered by behavior. Drinking large amounts of alcohol will reduce the biological half-life of water in the body. This has been used to decontaminate patients who are internally contaminated with tritiated water. The basis of this decontamination method is to increase the rate at which the water in the body is replaced with new water. The removal of ethanol (drinking alcohol) through oxidation by alcohol dehydrogenase in the liver from the human body is limited.

About this result

This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.

Related publications (3)

Related people (3)

Related units (1)

Related concepts (56)

Related courses (3)

Related lectures (11)

CH-604: Medicinal chemistry: concepts and case studies from the pharmaceutical industry

We will cover key concepts of Medicinal Chemistry, from identification of active chemical starting points to how they are optimized to deliver drug candidates. We will use real case studies from the p

BIO-478: Pharmacology and pharmacokinetics

This course introduces the student to the fudamentals of pharmacology, pharmacokinetics and drug-receptor interactions. It discusses also pharmacogenetics and chronopharmacology, to exemplify the chal

CH-332: Medicinal chemistry

Sitting at the crossroad of organic chemistry and medicine, this course outlines how an initial hit compound transitions into a lead candidate, and ultimately a drug, in the modern drug discovery worl

Cytokine engineering for targeted cancer immunotherapy

Li Tang, Lucia Bonati

Cytokines are key modulators of the immune responses and represent promising therapeutics for a variety of cancers. However, successful translation of cytokine-based therapy to the clinic is limited by, among others, severe toxicities and lack of efficacy due to cytokine pleiotropy and off-target activation of cells. Engineering cytokines with enhanced therapeutic properties has emerged as a promising strategy to overcome these challenges. Advances in protein engineering and protein-polymer conjugate technologies have fostered the generation of cytokines with enhanced target cell specificity and longer half-life than the native ones. These novel cytokines exhibit reduced systemic toxicities while focusing the activities at the tumor site, thus, enhancing antitumor immunity. The growing toolbox of cytokine engineering strategies will further stimulate the development of smart cytokine-based immunotherapies with enhanced efficacy and safety profiles.

2021

Non-covalent albumin-binding ligands for extending the circulating half-life of small biotherapeutics

Alessandro Angelini, Alessandro Zorzi, Sara Linciano

Peptides and small protein scaffolds are gaining increasing interest as therapeutics. Similarly to full-length antibodies, they can bind a target with a high binding affinity and specificity while remaining small enough to diffuse into tissues. However, despite their numerous advantages, small biotherapeutics often suffer from a relatively short circulating half-life, thus requiring frequent applications that ultimately restrict their ease of use and user compliance. To overcome this limitation, a large variety of half-life extension strategies have been developed in the last decades. Linkage to ligands that non-covalently bind to albumin, the most abundant serum protein with a circulating half-life of similar to 19 days in humans, represents one of the most successful approaches for the generation of long-lasting biotherapeutics with improved pharmacokinetic properties and superior efficacy in the clinic.

ROYAL SOC CHEMISTRY2019

Development of an albumin-binding ligand for prolonging the plasma half-life of peptide therapeutics

Alessandro Zorzi

Peptides represent a promising format for the development of therapeutics since they combine the advantages of proteins and small molecules. Several techniques based on rational design or in vitro evolution can be used to develop peptides as therapeutics. A limitation of peptides is a rapid clearance from the blood circulation when applied intravenously, preventing their application in therapies that require prolonged drug exposure. Several methods have been tested to extend the in vivo half-life of peptides, including fusion to long-lived serum proteins, PEGylation and conjugation to non-covalent albumin-binding ligands. A particularly attractive approach is a âpiggy backâ strategy in which peptides bind via a ligand to albumin without increasing significantly their small size. Acylation with fatty acids is the most successful strategy for delaying peptide clearance. The attachment of either myristic or palmitic acid to insulin and GLP-1 led to the approval of three acylated peptide drugs as daily injectable. Nevertheless, acylated conjugates generally present low solubility and weak affinity for albumin. Peptides have been explored as an alternative, as their format offers multiple approaches for affinity maturation as well as an easier synthesis of the conjugates. However, the albumin-binding peptides developed so far do not overcome the disadvantages faced with fatty acids. The first aim of my project was the development of an albumin-binding tag that combines the favorable properties of both fatty acids and peptides, and overcomes at the same time their limitations. This tag was engineered in order to have i) a high affinity for human albumin, ii) a high solubility in physiological solutions, and iii) an efficient synthesis in conjunction with therapeutic peptides. Towards this goal, I created a chimeric format consisting of a fatty acid combined with a short linear peptide. After iterative rounds of affinity screening, an evolved peptide-fatty acid tag able to bind human, rat and rabbit albumin with Kd values of 39, 220 and 320 nM, respectively, was obtained. This makes it the best albumin-binding tag among all of the peptide- or fatty acid-based ligands that have been developed. This tag can be easily synthesized in conjugation with peptides on standard automated synthesizers. Finally, it exhibits a high solubility due to four negatively charged amino acids in the peptide sequence, despite the presence of a 16-carbon palmitic hydrophobic tail. The second aim of my project was the application of this tag to three bioactive bicyclic peptides, previously developed in the laboratory, in order to improve their in vivo half-lives. I demonstrated that the conjugation has, overall, a mild impact on peptidesâ binding affinity towards their targets and human albumin, and increases their proteolytic stability. Pharmacokinetic experiments showed that the tag extends the elimination half-life of bicyclic peptides in rats and rabbits approximately 25-fold to over seven and five hours, respectively. Tag conjugation to a bicyclic peptide targeting coagulation factor XII led to an efficient inhibition of coagulation in rabbits up to eight hours, suggesting a potential application in humans as anti-thrombotic drug. These results indicated that the tag will efficiently prolong the exposure of target proteins to bioactive peptides in humans due to its higher affinity for human albumin than that of rat and rabbit.

EPFL2017

Pharmacokinetics

Pharmacokinetics (from Ancient Greek pharmakon "drug" and kinetikos "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body.

Biological half-life

Clearance (pharmacology)

In pharmacology, clearance is a pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time. Usually, clearance is measured in L/h or mL/min. The quantity reflects the rate of drug elimination divided by plasma concentration. Excretion, on the other hand, is a measurement of the amount of a substance removed from the body per unit time (e.g., mg/min, μg/min, etc.). While clearance and excretion of a substance are related, they are not the same thing.

Potential Flows: Basics and Applications ME-280: Fluid mechanics (for GM)

Introduces potential flows, stagnation points, superposition techniques, and flow around a cylinder.

Pharmacokinetic & Pharmacodynamic Evaluations CH-332: Medicinal chemistry

Covers the principles of pharmacokinetics and pharmacodynamics, including drug exposure-response relationships.

Pharmacokinetics Modeling: Zero and First-Order Kinetics BIO-478: Pharmacology and pharmacokinetics

Explores pharmacokinetics modeling, covering zero and first-order kinetics, drug distribution, and key parameters for drug elimination.