Cholinesterase inhibitors: applying pharmacokinetics to clinical decision making.

Overview

BACKGROUND: Cholinesterase inhibitors are indicated for the treatment of Alzheimer-type dementia. There are few direct comparative studies of adverse effects or studies to suggest clinical superiority of one inhibitor over the others. OBJECTIVE: The objective of this study was to relate pharmacokinetic differences among the agents to potential clinical considerations. METHODS: Population pharmacokinetics were obtained from US Food and Drug Administration-approved label information and published literature. Plasma concentration-time profiles were derived from these parameters using noncompartmental pharmacokinetic modeling. RESULTS: Plasma concentration profiles differed significantly among different agents and between different formulations of the same agent. CONCLUSIONS: The initial choice among the various cholinesterase inhibitors requires consideration to adherence and cost. Consideration to differences in pharmacokinetics among these drugs provides a better understanding for the clinical practice of dose titration, identification and management of drug-related side effects, and lapses in therapy. Pharmacokinetic considerations among the various agents and formulations provide the clinician with options to enhance therapy when these agents are chosen for treatment of patients with Alzheimer-type dementia.