| Abstrakt: |
Aims To assess whether renal impairment influences the pharmacokinetics of ziprasidone, and to determine whether ziprasidone is cleared via haemodialysis. Methods Thirty‐nine subjects with varying degrees of renal impairment were enrolled into an open‐label, multicentre, multiple‐dose study and assigned to four groups according to their renal function: normal (group 1, creatinine clearance > 70 ml min- 1); mildly impaired (group 2, creatinine clearance 30–60 ml min- 1); moderately impaired (group 3, creatinine clearance 10–29 ml min- 1), and severely impaired (group 4, requiring haemodialysis three times‐a‐week). Subjects received ziprasidone 40 mg day- 1, given orally with food, as two divided daily doses for 7 days and a single 20 mg dose on the morning of day 8. Pharmacokinetic variables were determined from multiple venous blood samples collected on days 1 and 8 (haemodialysis day for subjects with severe renal impairment). Additional samples were collected from subjects with severe renal impairment on day 7 (nonhaemodialysis day). Results On day 1 there were no statistically significant differences in the pharmacokinetics (AUC(0,12 h), Cmax, tmax) of ziprasidone among subjects with normal renal function and those with mild, moderate and severe renal impairment. The AUC(0,12 h) and Cmax in subjects with mildly impaired renal function were statistically significantly greater than in those with moderately impaired renal function (P= 0.0163–0.0385). The mean AUC(0,12 h) was 272, 370, 250 and 297 ng ml-1 h in groups 1, 2, 3 and 4, respectively. Corresponding mean Cmax values were 47, 61, 41 and 50 ng ml- 1 and corresponding mean tmax values were 5, 6, 5 and 5 h. On day 8 there were no statistically significant differences in the pharmacokinetics... [ABSTRACT FROM AUTHOR] |
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