PHARMACOKINETICS OF AN INDOMETHACIN PRO-DRUG - APYRAMIDE AFTER INTRAVENOUS ADMINISTRATION IN DOG

The pharmacokinetics of apyramide, an ester of indomethacin and acetam inophen (paracetamol), were determined after intravenous administratio n to nine beagle dogs. Indomethacin and its pro-drug, apyramide, were extracted from acetonitrile-precipitated plasma by a solvent-demixing procedure and the concentration of these two drugs was measured by a r eversed-phase liquid chromatographic assay. The kinetic evolution with time of plasma levels of apyramide and of indomethacin resulting from enzymatic hydrolysis was compared with values obtained for indomethac in injected in equimolar dose. Plasma levels of apyramide quickly decr eased and the mean (+/- SD) half life was 0.15 +/- 0.08 h. For metabol ic indomethacin, the mean (+/- SD) area under curve was 12.36 +/- 4.80 mg.h/l and the mean (+/- SD) half life of terminal phase was 16.71 +/ - 9.46 h. After administration of indomethacin, these values were 17.6 0 +/- 4.12 mg.h/l and 7.89 +/- 2.20 h, respectively.