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, including mice, rats, dogs, mini-pigs, and baboons, after administration of [14C]meloxicam. The plasma concentration-time profiles for meloxicam in rats and dogs were comparable to that in humans, whereas there were marked differences between humans and mice, mini-pigs, and baboons. The highest tissue concentrations of meloxicam in rats and mini-pigs were seen in the liver and kidneys. In contrast, low concentrations of meloxicam 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 the feces. As in humans, meloxicam circulated mainly in the form of the parent compound in the plasma of mice, rats, dogs, mini-pigs, and baboons. The main metabolites in rats, mini-pigs, and humans were a 5'-hydroxymethyl 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 profile of meloxicam in rats most closely resembles that in humans; therefore, reliable clinical predictions can be made from studies in this rodent species.
Busch
U
U
Department of Pharmacokinetics, Boehringer Ingelheim Pharma KG, 65, D-88397 Biberach an der Riss, Germany.
Schmid
J
J
Heinzel
G
G
Schmaus
H
H
Baierl
J
J
Huber
C
C
Roth
W
W
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004285:Dogs; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D000077239:Meloxicam; D051379:Mice; D010215:Papio; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature; D013843:Thiazines / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D013843:Thiazines; D013844:Thiazoles; D003577:Cytochrome P-450 Enzyme System; D000077239:Meloxicam