Abstract
We have investigated the interaction of azapropazone with phenytoin in five healthy volunteers. From steady-state plasma phenytoin concentrations of about 17 mumol/l there was at least a two-fold increase following the introduction of azapropazone. The main mechanism of the interaction was a decrease in phenytoin clearance, attributable to competitive inhibition by azapropazone of phenytoin p-hydroxylation. Protein-binding of phenytoin in the plasma (as assessed by salivary phenytoin concentrations) was significantly reduced from 92 to 90% by azapropazone and similar changes occurred in in vitro studies of [3H]-phenytoin protein binding.
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