RT Journal Article
SR Electronic
T1 Pharmacokinetics of Meloxicam in Animals and The Relevance to Humans
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 576
OP 584
VO 26
IS 6
A1 Ulrich Busch
A1 Jochen Schmid
A1 Günther Heinzel
A1 Helmut Schmaus
A1 Jürgen Baierl
A1 Claudia Huber
A1 Willy Roth
YR 1998
UL http://dmd.aspetjournals.org/content/26/6/576.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics