European journal of internal medicine · 2007
Aspirin esterase activity - Evidence for skewed distribution in healthy volunteers.
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Adebayo G I, Williams J, Healy S
Аннотация
BACKGROUND: Aspirin, with its analgesic, anti-inflammatory, antipyretic, and anti-platelet actions, is one of the most frequently used drugs. Although its use as prophylaxis against thromboembolism is well established, an optimal dose, conferring maximal anti-platelet action without increased risk of bleeding, remains elusive.
METHOD: We assessed the possible pharmacokinetic contribution to this problem in 107 healthy, non-medicated volunteers. Serum aspirin esterase activity was evaluated at 37 degrees C with 1 mM aspirin as substrate. On the basis of the report that most of aspirin esterase activity is accounted for by pseudocholinesterase, we additionally quantified the activity of this enzyme, with and without dibucaine as an inhibitor, using Ellman's reaction, in 41 of our volunteers.
RESULTS: Aspirin esterase activities in all of our volunteers (33.90 nmol/ml/min to 222.65 nmol/ml/min, median 103.45 nmol/ml/min) showed a continuous and skewed distribution with eight outliers. In the 41 subjects so studied, aspirin esterase activities correlated positively with both pseudocholinesterase activities (Spearman's rho=0.593, p<0.001) and dibucaine numbers (Spearman's rho=0.422, p<0.01).
CONCLUSIONS: Our results support previous observations that the rate of aspirin hydrolysis is not determined by aspirin esterase alone and that other factors are probably involved. Additionally, the skewed distribution of aspirin esterase activities makes a case for its possible contribution to the phenomenon of aspirin resistance.
METHOD: We assessed the possible pharmacokinetic contribution to this problem in 107 healthy, non-medicated volunteers. Serum aspirin esterase activity was evaluated at 37 degrees C with 1 mM aspirin as substrate. On the basis of the report that most of aspirin esterase activity is accounted for by pseudocholinesterase, we additionally quantified the activity of this enzyme, with and without dibucaine as an inhibitor, using Ellman's reaction, in 41 of our volunteers.
RESULTS: Aspirin esterase activities in all of our volunteers (33.90 nmol/ml/min to 222.65 nmol/ml/min, median 103.45 nmol/ml/min) showed a continuous and skewed distribution with eight outliers. In the 41 subjects so studied, aspirin esterase activities correlated positively with both pseudocholinesterase activities (Spearman's rho=0.593, p<0.001) and dibucaine numbers (Spearman's rho=0.422, p<0.01).
CONCLUSIONS: Our results support previous observations that the rate of aspirin hydrolysis is not determined by aspirin esterase alone and that other factors are probably involved. Additionally, the skewed distribution of aspirin esterase activities makes a case for its possible contribution to the phenomenon of aspirin resistance.