In vitro studies have shown that CYP3A4 is zibotentan for metabolism. Moreover, when administered in combination with itraconazole zibotentan, a potent CYP3A4 inhibitor, increased, Hte AUC by 28%. Hence, patients with hepatic or Nierenfunktionsst Evodiamine Isoevodiamine Zibotentan distance changes, the m May receive a gr Eren commitment zibotentan lead k Have reduced Nnte. A significant proportion of patients with CRPC have probably different degrees of renal failure due to urinary tract obstruction and flow of the tumor after prior chemotherapy. These findings support the assessment of the effects of renal or hepatic impairment on the pharmacokinetics of zibotentan. Pharmacokinetic parameters zibotentan healthy subjects Similar between the two studies and the results were consistent with previous pharmacokinetic studies.
In patients with mild RESTRICTION Nkter liver function or m Strength to severe renal impairment, there was no significant difference in the Cmax of zibotentan after a single oral dose of 10 mg zibotentan on these GW 791343 issues indicates normal with the function body, the absorption on has changed. Hepatic or renal function, however, was increased significantly Hen exposure zibotentan zibotentan following the slowdown distance. Beyond Hte exposure increased with the degree of hepatic or renal function. It is pointed out in the study of liver function, the pharmacokinetic profile of a subject, the mild adversely Chtigung group Similar to the PK profile of the patients in the severe and therefore the person will have an effect, the average values for the PK group and helped smooth the variability observed t.
Tats Chlich when this item was removed from the analysis, the upper confidence limit of the ratio fell Ltnisses AUC treatment below the preset limit of 2 In both studies, a Erh The half-life of zibotentan increased the degree of hepatic or renal function increase Ht, although this is more apparent in patients with limited Nkter liver function. Liver and kidney has been shown that Ver changes In plasma protein binding, therefore, the unbound fraction was calculated zibotentan 3 hours after administration cause free Cmax AUC and free unbound determine CL / F. Few Changes in the protein between the groups has been documented in both studies, and therefore no Cmax, AUC and free unbound CL / F change for all groups were similar Ver changes in Cmax, AUC, and CL / F. Data from the study showed that the liver, although mild to m strength had only a minor effect on the pharmacokinetic profile of zibotentan, the impact of the severe Leberfunktionsst ments was much gr it.
Total plasma clearance of zibotentan in persons with severe Restrict Restriction of liver function was 64% lower than subjects with normal function, which then results in an increase of approximately 190% exposure to zibotentan. In the three groups with Leberfunktionsst Ments, there was a large variability e t. Although the average increase Erh Exposure was 40 to 45% for light and m Moderately RESTRICTION Nkter groups, an increase of more than 2 can not be excluded. For the heavily adversely Chtigt group recorded an increase of 4.5 times can not be excluded. Data from the study showed that lighter Nierenfunktionsst insurance Only a minor effect on the pharmacokinetic profile of zibotentan had increased an average exposure of 66% Ht and the upper CI remaining under 2, w While In this case, the impats of moderate and severe renal insufficiency was increasingly important.