Simeprevira pharmacokinetic properties were evaluated in adult healthy volunteers and adult patients infected with hepatitis C. The anadrol 50mg plasma and area under the curve “concentration-time» after multiple dosing at the doses from 75 mg to 200 mg 1 time day increased more than proportionally to the dose; after repeated administration of the drug was observed its accumulation. The equilibrium state is achieved after 7 days of 1 times a day. Simeprevira concentration in plasma infected with hepatitis C virus patients is 2-3 times higher than the corresponding values in healthy volunteers. The values simeprevira plasma when combined with peginterferon alfa and ribavirin and as monotherapy simeprevirom were similar.
The average value of simeprevira bioavailability after a single dose of 150 mg orally dose during meals is 62%. The maximum plasma concentration is typically achieved after 4-6 hours after ingestion. Studies in vitro on Caco-2 human cell culture showed that simeprevir substrate .
The impact of food on the bioavailability of simeprevira
As compared with the reception fasting when receiving simeprevira during meal in healthy volunteers increased by 61% after the high energy breakfast high fat (928 kcal) and at 69% after breakfast normal caloric content (533 kcal), while there was an increase in absorption time 1 and 1.5 hours, respectively.
Simeprevir largely bound to plasma proteins anadrol 50mg, mostly to albumin and to a lesser extent? 1 acid glycoprotein. In patients with impaired renal or hepatic function significant changes in plasma protein binding is not registered. Animals simeprevir largely enters the intestine and liver (ratio of the content in the blood and liver of rats 29: 1).
Simeprevir metabolized in the liver. According to studies in vitro on human liver microsomes simeprevir predominantly undergoes oxidative metabolism by means of the liver isoenzyme . You also can not exclude the participation of isoenzymes .
Information about the effects of inhibitors or inducers isoenzymes with regard to pharmacokinetics simeprevira, as well as information about simeprevira inhibitory potential against isoenzymes in the section “Interaction with other drugs.”
After a single oral administration anadrol 50mg simeprevira at a dose of 200 mg in healthy volunteers, most of the radioactivity in the plasma (98%) represented the unmodified drug, and only a small proportion represented metabolites (none of which was not a significant metabolite). Identified fecal metabolites formed by oxidation of the macrocyclic or aromatic groups or both groups, as well as by O-demethylation followed by oxidation.
Withdrawal simeprevira occurs in the bile. The kidneys play a minor role in the removal of the drug. After a single oral administration of 14 C simeprevira at a dose of 200 mg in healthy volunteers, an average of 91% of the radioactive substances released through the intestines, <1% of the dose is excreted by the kidney. Unchanged simeprevir in feces was on average 31% of the dose.
The half-life simeprevira when receiving a dose of 200 mg in healthy volunteers was 10-13 hours, and patients infected with hepatitis C – 41 hours.
Special patient groups
Children (under 18 years)
Studies on the pharmacokinetics simeprevira not been conducted in children.
There is limited data on the use of the drug Sovriad in patients older than 65 years. Based on a population pharmacokinetic analysis in infected hepatitis C virus patients receiving simeprevir, age (18-73 years) had no clinically meaningful effect on the pharmacokinetics of simeprevira. In elderly patients, a dose adjustment is required.