Abstract
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.
Footnotes
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Send reprint requests to: Dr. Ulrich Busch, Boehringer Ingelheim Pharma KG, Birkendorfer Straβe 65, D-88397 Biberach an der Riss, Germany.
- Abbreviations used are::
- NSAID
- nonsteroidal anti-inflammatory drug
- CL
- clearance of drug from plasma
- Cmax
- maximum concentration of drug in plasma
- F
- bioavailability factor
- id
- intraduodenal
- MRT
- mean residence time
- Vss
- apparent volume of distribution under steady-state conditions
- tmax
- time to reach the maximum concentration of drug in plasma
- Vz
- apparent volume of distribution during the terminalλz phase
- λz
- terminal elimination rate constant
- Vss
- apparent volume of distribution under steady-state conditions
- CYP
- cytochrome P450
- Received June 20, 1997.
- Accepted February 9, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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