Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor.
Acetaminophen acts functionally as a selective COX-2 inhibitor led us to investigate the hypothesis of whether it works via preferential COX-2 blockade. In vitro, acetaminophen elicited a 4.4-fold selectivity toward COX-2 inhibition (IC(50)=113.7 micromol/L for COX-1; IC(50)=25.8 micromol/L for COX-2). Following oral administration of the drug,
maximal ex vivo inhibitions were 56% (COX-1) and 83% (COX-2). Acetaminophen plasma concentrations remained above the in vitro IC(50) for COX-2 for at least 5 h postadministration. Ex vivo IC(50) values (COX-1: 105.2 micromol/L; COX-2: 26.3 micromol/L) of acetaminophen compared favorably with its in vitro IC(50) values. In contrast to previous concepts, acetaminophen inhibited COX-2 by more than 80%, i.e., to a degree comparable to nonsteroidal antiinflammatory drugs (NSAIDs) and selective COX-2 inhibitors. However, a >95% COX-1 blockade relevant for suppression of platelet function was not achieved [1]. |
