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.
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http://dx.doi.org/10.1046/j.1365-2125.1998.0460s1056.x | DOI Listing |
J Neurophysiol
January 2025
Dept of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Deep brain stimulation (DBS) using electrical stimulation of neuronal tissue in the basal forebrain to enhance release of the neurotransmitter acetylcholine is under consideration to improve executive function in patients with dementia. While some small studies indicate a positive response in the clinical setting, the relationship between DBS and acetylcholine pharmacokinetics is incompletely understood. We examined the cortical acetylcholine response to different stimulation parameters of the basal forebrain.
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February 2025
Department of Biosciences, COMSATS University Islamabad (CUI), Park Road, Islamabad, 45550, Pakistan. Electronic address:
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View Article and Find Full Text PDFPharmacol Res Perspect
December 2024
Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Acetylcholinesterase inhibitors (AChEIs) remain the first-line treatment for Alzheimer's disease. However, these drugs are largely symptomatic and often associated with adverse effects. This study aimed to evaluate novel pharmacophores for their in vitro AChEI activity, blood-brain barrier (BBB) permeability, and cytotoxic potential, hypothesizing that a combination of AChEIs could enhance symptom management while minimizing toxicity.
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December 2024
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
Donepezil (DNP) is a selective cholinesterase inhibitor widely used for the therapy of Alzheimer's disease. Instances of liver injury correlated with DNP treatment have been reported, yet the underlying hepatotoxic mechanism remains to be elucidated. This study aimed to explore the contribution of metabolic activation to the hepatotoxicity of DNP.
View Article and Find Full Text PDFMol Pharm
December 2024
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning, China.
Novel hydroxyphenyl adhesives (HP-PSAs) could significantly increase drug solubility and control drug release through a doubly ionic hydrogen bond (DIH bond) in the patch. However, chemical penetration enhancers (CPEs) always destroy the performance of most adhesives. As a result, this work investigated the stability of both the HP-PSA features and the DIH bond under the interference of the CPEs.
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