Insulin half-life

Ultra-short-acting insulin (half-life 0.5-2 hours)... 

Insulin formulation Ultra-short-acting Insulin (half-life 0.5-2 hours) Regular Insulin (half-life 2-4 hours) Intermediate-acting Insulin (half-life 16-20 hours) Prolonged-acting insulin (half-life 36 hours and over) Intraindividual variation In absorption up to 50% Interindividual variation from day-to-day up to 25%... 

DPP-4 is a serine protease that inactivates GLP-1. GLP-1 stimulates insulin secretion and suppresses glucagon release. The inhibition of DPP-4 prolongs the half-life of GLP-1 and brings about beneficial effects on glucose levels and glucose tolerance in type 2 diabetics. Backes et al. [64] report on the parallel optimization of enzyme binding affinity and inhibition, selectivity, ADME properties, and PK (Scheme 19). 

Somatostatin. Somatostatin is an endogenous peptide hormone involved in e.g. the control of the release of Somatomedin, Insulin and Pancreatin. Due to its biological role, Somatostatin has a very low biological stability. The half-life in the rabbit after intravenous administration has been determined to approximately 90 seconds in this investigation. After sc or im administration, the apparent half-life is somewhat longer, close to 10 minutes, probably due to the absorption of the peptide from the injection site into the systemic circulation. 

Insulin, at typical normal plasma concentrations (approximately 1 x 10-9 mol l-1) exists in true solution as a monomer. Any insulin injected directly into the bloodstream exhibits a half-life of only a few minutes. 

A number of studies have also focused upon the generation of longer-acting insulin analogues. The currently used Zn-insulin suspensions, or protamine-Zn-insulin suspensions, generally display a plasma half-life of 20-25 h. Selected amino acid substitutions have generated insulins which, even in soluble form, exhibit plasma half-lives of up to 35 h. 

An apparently more effective method for prolonging the half-life of insulin in the blood is to add substituents at the end of the A- or B-chain (or both) that alter the chemical properties of the molecule and delay its breakdown in the body. A product known as HOE 901 (insulin glargine) has two glycine residues added to one end of the B-chain and the A21 asparagine residue replaced with another glycine residue. These changes modify the acidity of the insulin molecule, reducing the rate at which it is absorbed and metabolized in the body. 

In the body, insulin is synthesized by j3-cells of Langerhans islets in the pancreas. The rate of formation changes depending on the type of food consnmed, gastrointestinal hormones, and nenronal control. Insnlin circnlating in the body has a biological half-life of about 5 min. It is qnickly broken down by enzymes and is removed from the blood by the liver or kidneys. 

Insulin preparations Half-life Onset Peak Duration Compatible... 

Insulin is removed from the circulation by the liver and the kidney. The disulfide connections between the A and B chains are hydrolyzed through the action of glutathione insulin trans-hydrogenase. After this cleavage further degradation occurs by proteolysis. In patients treated with subcutaneous insulin injections the clearance by the liver is 40% and by the kidney 60%. The half-life of circulating insulin is 3-5 min. 

Octreotide acetate (Sandostatin) is a synthetic peptide analogue of the hormone somatostatin. Its actions include inhibition of the pituitary secretion of growth hormone and an inhibition of pancreatic islet cell secretion of insulin and glucagon. Unlike somatostatin, which has a plasma half-life of a few minutes, octreotide has a plasma elimination half-Hfe of 1 to 2 hours. Excretion of the drug is primarily renal. 

Mechanism of Action Afirst-generation sulfonylurea that promotes release of insulin from beta cells of pancreas. Therapeutic Effect Lowers blood glucose concentration. Pharmacokinetics Rapidly absorbed from the gastrointestinal (Gl) tract. Protein binding 60%-90%. Extensively metabolized in liver. Excreted primarily in urine. Removed by hemodialysis. Half-life 30-42 hr. 

It is a peptide containing 14 amino acids and inhibits the release of growth hormone, TSH and prolactin from the pituitary and insulin and glucagon in pancreas. It has a very short plasma half-life. Because of its shorter duration of action and lack of specificity in inhibiting only GH secretion, its use in the treatment of acromegaly is limited. 

Insulin is not given orally. After IV or SC injection, it circulates as free, monomer in blood and has a short plasma half life. Insulin is degraded mainly in liver, muscle and kidney. 

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