After oral administration, dapagliflozin is rapidly and completely absorbed in the gastrointestinal tract and can be taken with meals, and outside of it. Dapagliflozin Maximum concentration in blood , the plasma is usually reached within 2 hours after the fasting. The values of buy trenbolone acetate (area under the curve of concentration vs. time) increases in proportion to the dose of dapagliflozin. The absolute bioavailability of dapagliflozin when taken orally at a dose of 10 mg is 78%. Food intake has a moderate effect on the pharmacokinetics of dapagliflozin in healthy volunteers.Eating a high-fat diet reduced the dapagliflozin Cmax by 50%, prolongs Tmax (time to maximum plasma concentration) for about 1 hour, but had no effect, compared to the fasting state. These changes are not clinically significant.
Distribution dapagliflozin approximately 91% bound to protein. In patients with various diseases, such as impaired renal or hepatic function, this parameter was not changed. Metabolism dapagliflozin – C-linked glucoside aglycone which is associated with glucose carbon-carbon bond, which ensures its stability against glucosidases. The average half-life in blood plasma from healthy volunteers was 12.9 hours after receiving a single oral dose of dapagliflozin 10 mg. Dapagliflozin is metabolised to form mainly the inactive metabolite of dapagliflozin-3-O-glucuronide.After oral administration of 50 mg 14C-dapagliflozin 61% of the dose is metabolized in the dapagliflozin-3-O-glucuronide, which accounted for 42% of the total plasma radioactivity – The share of unchanged drug accounted for 39% of total plasma radioactivity. Shares of other metabolites individually do not exceed 5% of the total plasma radioactivity. Metabolites have no pharmacological effect. Is formed by the enzyme uridine diphosphate-glucuronosyltransferase present in the liver and kidney cytochrome involved in the metabolism of a lesser degree.
Excretion dapagliflozin and its metabolites are excreted mainly by the kidneys, and less than 2 % is excreted unchanged. After taking 50 mg of 14 C-dapagliflozin 96% of the radioactivity was found – 75% in urine and 21% – in the feces. Approximately 15% of the radioactivity detected in the feces accounted for dapagliflozin unchanged.
Pharmacokinetics in special clinical situations Patients with renal impairment In the equilibrium state buy trenbolone acetate systemic exposure dapagliflozin in patients with type 2 diabetes and renal light failure, moderate or severe (as determined by the clearance of iohexol) was 32%, 60% and 87% higher than that in patients with type 2 diabetes and normal renal function, respectively. The amount of glucose outputted kidney overnight at reception dapagliflozin in an equilibrium state dependent on the state of renal function. Patients with type 2 diabetes and normal renal function and renal insufficiency mild, moderate or severe excreted in 85 hours, 52, 18, and 11 g of glucose, respectively. There were no differences in the binding of dapagliflozin with proteins in healthy volunteers and in patients with renal failure of varying severity. It is not known whether hemodialysis has an impact on the exposure dapagliflozin. Patients with hepatic impairment In patients with hepatic impairment or mild to moderate severity averages dapagliflozin were, respectively, 12% and 36% higher compared with healthy volunteers.