Open AccessThe Relative Roles of Hydrolases of the Erythrocyte and Other Tissues in Controlling Aspirin Survival in Vivo
Author(s) -
Costello Patrick B.,
Caruana Joseph A.,
Green Floyd A.
Publication year - 1984
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780270409
Subject(s) - in vivo , hematocrit , aspirin , esterase , thrombocytosis , pharmacology , chemistry , splenectomy , whole blood , medicine , immunology , endocrinology , platelet , biochemistry , enzyme , spleen , biology , microbiology and biotechnology
The rate of aspirin (acetyIsalicylic acid, ASA) deacetylation to salicylate in vivo determines the availability of the intact molecule for therapeutically important transacetylation reactions. Experiments were carried out to assess the relative contribution of a previously isolated human erythrocyte ASA esterase to the overall hydrolysis rate in vivo, as opposed to similar enzymes in other tissues. In vitro, the rates of ASA hydrolysis were relatively slow in plasma from humans and dogs. The hydrolysis rates were significantly greater in whole blood in dogs, rabbits, and humans. In human and canine whole blood, the rate of hydrolysis correlated positively with hematocrit. In vivo studies with dogs showed that ASA decay rates conform to a 2‐compartment model. After reduction of hematocrit by a mean of 49% in 4 dogs without previous splenectomy, the “availability” of ASA increased. In 4 dogs with previous splenectomy, this measurement was increased even more after comparable hematocrit reduction. In 2 dogs that underwent a sub‐total hepatectomy, ASA availability increased by only 35% and 12.8%, respectively. These results suggest a significant role for the erythrocyte esterase in vivo in the dog and possibly in humans.