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An evaluation of the pharmacokinetics of donepezil HCl in patients with moderately to severely impaired renal function
Author(s) -
Paul J. Tiseo,
Karen Foley,
Lawrence Friedhoff
Publication year - 1998
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1998.0460s1056.x
Subject(s) - pharmacokinetics , donepezil , medicine , renal function , impaired renal function , pharmacology , urology , oral administration , dementia , disease
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 ). C max (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–∞) 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.