Liquid chromatographic-ultraviolet methods for furegrelate in serum and urine: preliminary pharmacokinetic evaluation in the dog.

Analytical methods have been developed for the quantitative determination of furegrelate (1), a thromboxane synthetase inhibitor, in dog serum and urine specimens. The methods use ion-pairing reversed-phase high-performance liquid chromatography (HPLC) with UV detection at 268 nm and have the necessary specificity, linearity, and sensitivity to quantitate 100 ng/mL of the drug in serum and 20 micrograms/mL in urine. Preliminary pharmacokinetic and bioavailability evaluations in the dog indicate that 1 was rapidly distributed and had a terminal half-life of 132 min after an intravenous dose. The primary route of elimination was renal with approximately 70% of the parent drug excreted in urine. Fasted dogs dosed orally with the drug in solution or capsule had similar absorption and elimination kinetics and agreed favorably with the intravenous results. The bioavailability of 1 dosed orally was 77-80% based on serum area under curve and greater than 90% based on urinary excretion of the parent compound. The serum kinetics, but not the urinary elimination, of 1 appeared to be altered in fed dogs given drug in capsule.