Ketosteril Mechanism of Action

Pharmacotherapeutic Group: Amino acids, including combinations with polypeptides. ATC Code: V06DD.
Pharmacology: Pharmacodynamics: Ketosteril tablets are administered for nutrition therapy in chronic kidney disease.
Ketosteril allows the intake of essential amino acids while minimising the amino-nitrogen intake.
Following absorption, the keto- and hydroxyanalogues are transaminated to the corresponding essential amino acids by taking nitrogen from non-essential amino acids, thereby decreasing the formation of urea by re-using the amino group. Hence, the accumulation of uraemic toxins is reduced. Keto- and hydroxy- acids do not induce hyperfiltration of the residual nephrons. Ketoacid-containing supplements exert a positive effect on renal hyperphosphatemia and secondary hyperparathyroidism. Moreover, renal osteodystrophy may be improved. The use of Ketosteril in combination with a very low protein diet allows to reduce nitrogen intake while preventing the deleterious consequences of inadequate dietary protein intake and malnutrition.
Pharmacokinetics: The plasma kinetics of amino acids and their integration in metabolic pathways are well established. It should nevertheless be noted that in uraemic patients, the cause of the changed plasma levels which occur frequently in these patients, does not seem to be the absorption of the supplied amino acids (ie, the absorption itself is not disturbed). The changed plasma levels seem to be due to impaired post-absorptive kinetics, which can be detected in a very early stage of the disease.
In healthy individuals, the plasma levels of ketoacids increase within 10 min after oral administration. Increases of up to 5-fold the baseline levels are achieved. Peak levels occur within 20-60 min and after 90 min, levels stabilise in the range of the base levels. Gastrointestinal absorption is thus very rapid. The simultaneous increase in levels of the ketoacids and the corresponding amino acids show that the ketoacids are transaminated very rapidly. Due to the physiological utilisation pathways of ketoacids in the body, it is likely that exogenously supplied ketoacids are very rapidly integrated into metabolic cycles. Ketoacids follow the same catabolic pathways as the classical amino acids. No specific study on ketoacid excretion has been performed to date.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies on pharmacological safety, acute and repeated dose toxicity, reproduction toxicity and genotoxicity. Ketosteril does not show teratogenic properties.