PHARMACOKINETICS OF MELOXICAM IN ANIMALS AND THE RELEVANCE TO HUMANS

The pharmacokinetic profile of the new nonsteroidal anti-inflammatory drug meloxicam was investigated in a number of animal species, includi ng mice, rats, dogs, mini-pigs, and baboons, after administration of [ C-14]meloxicam. The plasma concentration-time profiles for meloxicam i n rats and dogs were comparable to that in humans, whereas there were marked differences between humans and mice, mini-pigs, and baboons. Th e highest tissue concentrations of meloxicam in rats and mini-pigs wer e seen in the liver and kidneys. In contrast, low concentrations of me loxicam were found in the central nervous system, compared with those in plasma. The excretion balance in mini-pigs resembled that in humans , with almost equal concentrations being eliminated in the urine and t he feces. As in humans, meloxicam circulated mainly in the form of the parent compound in the plasma of mice, rats, dogs, mini-pigs, and bab oons. The main metabolites in rats, mini-pigs, and humans were a 5'-hy droxymethyl derivative (AF-UH 1 SE) and a 5'-carboxy metabolite (UH-AC 110 SE), The percentage of meloxicam binding to protein was higher in rats and humans (>99%) than in other species. The pharmacokinetic pro file of meloxicam in rats most closely resembles that in humans; there fore, reliable clinical predictions can be made from studies in this r odent species.