AIM: The aim of this study was to evaluate the pharmacokinetics of donepezil HCl (5 mg) in patients with moderately to severely impaired renal function (creatinine clearance: <30 ml min(-1) 1.73 m(-2)), following the administration of single oral doses. METHODS: This was an open-label, non-randomized study in patients with compromised renal function (n=11), and in age- and gender-matched healthy controls (n =11). Each subject received a single oral dose of 5 mg donepezil. Blood samples for pharmacokinetic measurements were taken at specified intervals for 17 days post-dose. Concentrations of donepezil in plasma were measured by HPLC with UV detection. RESULTS: There were no statistical differences between the two groups for any of the pharmacokinetic parameters evaluated (ANOVA). Cmax (mean +/- SD) was 7.7+/-1.2 ng ml(-1) in healthy subjects and 8.3+/-3.2 ng ml(-1) in renally impaired patients. AUC(0-infinity) in healthy subjects and in renally impaired patients was 539+/-115 ng h ml(-1) and 640+/-150 ng h ml(-1), respectively. The mean half-life of donepezil was 86.7+/-23.3 h in healthy subjects and 91.3+/-40.9 h in the renally impaired patients. The drug was well tolerated by all study participants. There were no clinically significant changes in vital signs, clinical chemistry or ECG parameters. CONCLUSIONS: These findings suggest that the pharmacokinetics of donepezil do not change in patients with moderately to severely impaired renal function.
AIM: The aim of this study was to evaluate the pharmacokinetics of donepezil HCl (5 mg) in patients with moderately to severely impaired renal function (creatinine clearance: <30 ml min(-1) 1.73 m(-2)), following the administration of single oral doses. METHODS: This was an open-label, non-randomized study in patients with compromised renal function (n=11), and in age- and gender-matched healthy controls (n =11). Each subject received a single oral dose of 5 mg donepezil. Blood samples for pharmacokinetic measurements were taken at specified intervals for 17 days post-dose. Concentrations of donepezil in plasma were measured by HPLC with UV detection. RESULTS: There were no statistical differences between the two groups for any of the pharmacokinetic parameters evaluated (ANOVA). Cmax (mean +/- SD) was 7.7+/-1.2 ng ml(-1) in healthy subjects and 8.3+/-3.2 ng ml(-1) in renally impaired patients. AUC(0-infinity) in healthy subjects and in renally impaired patients was 539+/-115 ng h ml(-1) and 640+/-150 ng h ml(-1), respectively. The mean half-life of donepezil was 86.7+/-23.3 h in healthy subjects and 91.3+/-40.9 h in the renally impaired patients. The drug was well tolerated by all study participants. There were no clinically significant changes in vital signs, clinical chemistry or ECG parameters. CONCLUSIONS: These findings suggest that the pharmacokinetics of donepezil do not change in patients with moderately to severely impaired renal function.
Authors: H Sugimoto; Y Tsuchiya; H Sugumi; K Higurashi; N Karibe; Y Iimura; A Sasaki; Y Kawakami; T Nakamura; S Araki Journal: J Med Chem Date: 1990-07 Impact factor: 7.446
Authors: Christa F Nagy; Dinesh Kumar; Edward I Cullen; W Kline Bolton; Thomas C Marbury; Maria J Gutierrez; H Wayne Hutman; Raymond D Pratt Journal: Br J Clin Pharmacol Date: 2004-11 Impact factor: 4.335