Abstract

The pharmacodynamics of non-steroidal anti-inflammatory drugs (NSAIDs) are for the most part well-understood. All NSAIDs inhibit the enzyme cyclooxygenase (COX), and for this reason prostaglandin synthesis. Two isoforms of COX could be isolated. COX-1 is detectable in most tissues on a constant level and is responsible for the synthesis of prostaglandins with cytoprotective effects. COX-2 is induced through inflammation and supports the inflammatory process by producing pro-inflammatory prostaglandins. The desired effects of NSAIDs are related to inhibition of COX-2, whereas inhibition of COX-1 has been linked to the typical side-effects of NSAIDs, especially in the stomach and kidney. The great differences between effects and side-effects in the numerous substances can be explained because of different interactions of the NSAIDs on COX-1 and COX-2. In various test systems meloxicam has been shown to be a preferential inhibitor of COX-2. There are also large differences between the individual NSAIDs with regard to pharmacokinetics. Meloxicam is completely absorbed from the gastrointestinal tract and has an elimination half-life of 24 hours in the dog. It is excreted in faeces and urine. The metabolites, detectable in urine are biologically inactive and do not influence the prostaglandin synthesis in the kidney. In the underlying study, plasma concentration of meloxicam was determined after a subcutaneous injection of 0.2 mg/kg b. w. (day 1) followed by oral treatment of 0.1 mg/kg b. w. (days 2-14). The results confirm the recommended dosage regime of meloxicam with its initial loading dose and the subsequent maintenance dose. This dosing regime results in a very favourable curve of concentrations with a very rapidly attained steady state after roughly two days, without accumulation even in long-term treatment.