A PATIENT-SIDE TECHNIQUE FOR REAL-TIME MEASUREMENT OF ACETYLCHOLINESTERASE ACTIVITY DURING MONITORING OF EPTASTIGMINE TREATMENT

Rapid and reliable measurement of acetylcholinesterase (AChE) activity is of crucial importance to the pharmacodynamic monitoring of anticho linesterase drugs. A new assay has been developed to measure AChE from 10 mu l samples of capillary blood. AChE activity was calculated from the change in pH of the reaction medium caused by the hydrolysis of a cetylcholine and measured with a highly sensitive differential pH appa ratus (CL-10, Eurochem, Rome, Italy). Interference by butyrylcholinest erase was eliminated by a specific inhibitor, quinidine sulfate. The a ssay lasts 1 min. The coefficient of variation (CV) for replicated mea surements was 2.8% (3267 U/L, n = 33). Linearity ranged from 0 to 10,0 00 U/L. The correlation coefficient between the new technique and Ellm an's colorimetric method on washed erythrocytes was r = 0.987 (y = 1.2 99x - 63, n = 29). The correlation coefficient between assays on capil lary and venous samples was r = 0.979 (y = 0.974x + 174, n = 47). A cr oss-laboratory validation study was performed in 10 centers using glyc erol-stabilized hemolysates with normal and reduced AChE activity. Sam ples were assayed in triplicate. The within- and between-laboratory CV s for samples with normal AChE activity (6,018 U/L) were 2.2 and 8.1%, respectively. The new method was applied to a double-blind, placebo-c ontrolled multicenter study of eptastigmine in Alzheimer patients and proved to be a simple, noninvasive, rapid, and reliable method for pha rmacodynamic monitoring of this drug.