The interaction of exendin (9-39)
Exendin (9-39) is an incretin hormone analogues, a constructed peptide (anti-hyperglycemic effect), 53% of its amino acerbic arrangement of glucagon-like polypeptide and the mammal -1 (GLP-1) and the the aforementioned amino acerbic sequence, but not GLP-1 analogs. GLP-1 is an abdominal hormone that is the abdominal L beef through its receptor hormone beard in acknowledgment to comestible intake, to aftermath hypoglycemic and anti-diabetic furnishings (e.g. activate glucose-dependent insulin release, inhibition of glucagon hormone secretion), but beneath half-life of beneath than 2 minutes, accelerated abasement by proteolytic enzymes (dipeptide lactamase )]. All pharmacodynamic furnishings of the biologic can be aflame GLP-1 receptor, constant in a agnate role with the GLP-1 [many (or all) of the anti-diabetic furnishings like in aggregate with GLP-1 receptor, but empiric with GLP- 1, the aftereffect is not consistent, advisers accept that this may be generated by the altered functions of added receptors of the drug]. Its furnishings include: added glucose-dependent insulin beard and arrest the aberrant access of the glucose-dependent glucagon secretion, apathetic belly emptying, abatement aliment intake, advance of beta-cell admeasurement and regeneration, abbreviation fat accession and insulin sensitizing aftereffect (animal models). As the biologic is almost aggressive to proteolytic enzymes IV (dipeptide lactamase ) abasement (due to the GLP-1, 2 attendance of an alanine group, the identification of a protein hydrolase , the biologic bit glycine group), it has a best half-life in vivo action compared with the GLP-1 enhanced. The biologic can be decidedly bargain claret glucose akin of the fasted state, abbreviation postprandial glucose aiguille aberration with account to baseline values; empiric afterwards dosing with delayed belly emptying, bargain calorie intake. The abstracts announce that in non-diabetic capacity and in patients with blazon 2 diabetes, the biologic is a almighty insulin beard drugs.
Exendin (9-39) is acclimated alone for subcutaneous injection. In the thigh, belly or high arm subcutaneous injection. To patients with blazon 2 diabetes subcutaneous bang of the drug, assuming lower postprandial glucose levels endure up to 5 hours, about 3 hours afterwards bang and accomplished the everyman point. Blazon 2 diabetic patients afterwards subcutaneous bang of 10 microg 2.1 hours aiguille assimilation (Cmax) 211pg/ml beneath the ambit (AUC) was 1.036 (ng h) / ml. Beastly studies, the bioavailability of the subcutaneous administering of 65% -75%, the aboriginal beastly bioavailability data. Subcutaneous and intravenous administering the aggregate of administration were 28.3L (nothing to do with the dose, age, gender, race, and the patient’s body) and 64ml/kg (healthy subjects). Biologic metabolism in bodies is unclear, but the beastly abstraction showed that the biologic of a proteolytic agitator is added aggressive to abasement as compared to GLP-1. The biologic austere by glomerular filtration, followed by proteolytic degradation, the boilerplate renal approval amount of 9.1L / h and the terminal half-life of 2.4 hours, balmy to abstinent renal crime (creatinine approval 30-80ml/min) The beggarly renal approval is bargain to 0.9L / h. The renal approval and half-life are absolute of dose, age, gender, race, and the patient’s body. Genetic and changeable toxicity beastly studies accept apparent that the adverse furnishings of drugs on the fetus (teratogenic, fetal afterlife or other). In aggregate with lovastatin, lovastatin can could could cause the AUC and aiguille claret assimilation and bioavailability is reduced. The apparatus may apathetic down belly elimination abbreviation the assimilation of the accordant could could cause of lovastatin. Aggregate may charge to access the the lovastatin dosage to atone for their bargain bioavailability and the charge to adviser claret lipids.