Darunavir is an inhibitor primobolan depot for sale of dimerization and catalytic activity of the protease of human immunodeficiency virus type 1 (HIV-1). The drug selectively inhibits cleavage of Gag-Pol polyproteins by HIV viruses in infected cells by preventing the formation of full virus particles. Darunavir binds strongly with HIV-1 protease . Darunavir is resistant to mutations causing resistance to protease inhibitors. Darunavir does not inhibit any of 13 tested human cellular proteases.
The pharmacokinetic properties of darunavir, is used in combination with ritonavir, were studied in healthy volunteers and in HIV-infected patients. Darunavir plasma concentrations were higher in patients infected with HIV-1 than in healthy people. This difference can be explained by higher concentrations of alpha 1-acid glycoprotein in patients infected with HIV-1, and therefore large amounts of darunavir bind to plasma alpha1-acidic glycoprotein. Darunavir metabolized mainly isozymes CYP3A4. Ritonavir inhibits CYP3A4 isozymes liver and thus considerably increases the concentration of darunavir in the plasma.
Absorbance After ingestion darunavir is rapidly absorbed in the gastrointestinal tract. Maximum plasma concentration of darunavir in the presence of low doses of ritonavir is reached after 2.5 -. 4.0 parts per dose The absolute bioavailability of darunavir (600 mg) at intake was approximately 37% and increased up to about 82% in the presence of ritonavir (100 mg of two times a day). Overall pharmacokinetic effect of ritonavir was approximately 14-fold increase in the concentration of darunavir in plasma after a single oral administration of 600 mg of darunavir in combination with ritonavir (100 mg twice a day). In the fasted relative bioavailability of darunavir in the presence of low doses of ritonavir was 30% lower than when receiving meals. Therefore, Prezista tablet ® should be taken with ritonavir with food. Character food did not affect the plasma concentration of darunavir. Distribution About 95% darunavir binds to plasma proteins, mainly to alpha 1-acid glycoprotein.
Metabolism In in vitro experiments on human liver microsomes showed that exposed predominantly darunavir oxidative metabolism. Darunavir primobolan depot for sale is extensively metabolized by the liver cytochrome P450 system, almost exclusively by isoenzyme CYP3A4. A study in which healthy volunteers received 14 C-darunavir showed that most of the radioactivity in plasma after a single administration of 400 mg of darunavir and ritonavir 100 mg accounted for by unchanged darunavir. A person is identified by at least 3 darunavir oxidative metabolite; Activity of these metabolites against wild-type HIV was less than 1/10 of the activity of darunavir. Excretion After a single dose of 400 mg 14 C-darunavir and ritonavir 100 mg of approximately 79.5% and 13.9% of the radioactivity was detected in the feces and urine, respectively, . The share unchanged darunavir accounted for approximately 41.2% and 7.7% of the radioactivity in faeces and urine, respectively. The final half-life of darunavir was approximately 15 hours when it is received in combination with ritonavir. The clearance of darunavir after intravenous administration of 150 mg was 32.8 l / h (without ritonavir) and 5.91 l / h in the presence of low dose ritonavir. Special populations Children The pharmacokinetics of darunavir in combination with ritonavir in children aged 6 to 18 years weighing not less than 20 kg is comparable to the pharmacokinetics in adult patients receiving Prezista ® / ritonavir 600/100 mg 2 times a day. Elderly patients Population pharmacokinetic analysis in HIV infected patients showed no significant differences in the pharmacokinetic parameters of darunavir in the age group 18 – 75 years (in the analysis of 12 HIV-infected patients aged 65 years and older were included). Sex differences Population pharmacokinetic analysis revealed slightly higher (16.8%) of the concentration of darunavir in HIV-positive women than in HIV-infected men. This difference is not clinically relevant.
Patients with impaired renal function results of the study with 14 C-darunavir with ritonavir showed that approximately 7.7% of the administered dose of darunavir excreted in the urine in unchanged form. Patients with impaired renal function, the pharmacokinetics of darunavir has not studied, but a population pharmacokinetic analysis showed no significant changes in pharmacokinetic parameters of darunavir in patients with moderate to severe renal function impairment (creatinine clearance of serum 30-60 ml / min, n = 20). Patients with impaired function liver Darunavir is metabolised and excreted mainly by the liver. In a study using multiple doses Prezista ® in combination with ritonavir (600/100 mg) twice a day has been shown that stable pharmacokinetic parameters of darunavir in patients with mild (Class A according to Child-Pugh, n = and moderate dysfunction liver (class B Child-Pugh, n = 8) were comparable with those parameters in healthy individuals. The effect of severe hepatic primobolan depot for sale impairment on the pharmacokinetics of darunavir has not been studied.
Treatment of HIV infection in adults and children aged 6 years and weighing 20 kg or more previously received antiretroviral therapy (in combination with low dose ritonavir and other antiretroviral agents).