Disposition of 4,5-diphenyl-2-oxazolepropionic acid (oxaprozin) in beagle dogs and rhesus monkeys.
Following intragastric doses of 14C-oxaprozin to beagle dogs and rhesus monkeys, oxaprozin was rapidly absorbed and was essentially the only drug-related substance in the plasma for at least 24 hr. Recovery of radioactivity in the excreta was 87% in both species, with the fecal route accounting for almost all of the excretion by the dog, and the urinary route predominating in the monkey. The drug was slowly eliminated by both species. The concentrations in tissues of monkeys were generally less than those in plasma, and their decline with time paralleled that in plasma. High concentrations of 14C were found in the bile and urine. Qualitative and quantitative metabolite patterns of both fluids were similar. About 90% of the 14C in both bile and urine was recovered as identified compounds in the free, ester conjugate, and ether conjugate fractions. The ester conjugate fraction, mainly consisting of oxaprozin glucuronide, was quantitatively the most important in both fluids. Two phenolic metabolites were characterized by mass spectrometry and co-chromatography. They were present in free form and as ester and ether glucuronides.
Disposition of 4,5-diphenyl-2-oxazolepropionic acid (oxaprozin) in beagle dogs and rhesus monkeys. Following intragastric doses of 14C-oxaprozin to beagle dogs and rhesus monkeys, oxaprozin was rapidly absorbed and was essentially the only drug-related substance in the plasma for at least 24 hr. Recovery of radioactivity in the excreta was 87% in both species, with the fecal route accounting for almost all of the excretion by the dog, and the urinary route predominating in the monkey. The drug was slowly eliminated by both species. The concentrations in tissues of monkeys were generally less than those in plasma, and their decline with time paralleled that in plasma. High concentrations of 14C were found in the bile and urine. Qualitative and quantitative metabolite patterns of both fluids were similar. About 90% of the 14C in both bile and urine was recovered as identified compounds in the free, ester conjugate, and ether conjugate fractions. The ester conjugate fraction, mainly consisting of oxaprozin glucuronide, was quantitatively the most important in both fluids. Two phenolic metabolites were characterized by mass spectrometry and co-chromatography. They were present in free form and as ester and ether glucuronides.