Efficacy and Tolerability of Meloxicam, a COX-2 Preferential Nonsteroidal Anti-Inflammatory Drug

M. Del Tacca, R. Colucci, M. Fornai, C. Blandizzi

Disclosures

Clin Drug Invest. 2002;22(12) 

In This Article

Pharmacokinetics

Meloxicam is well absorbed after oral administration, with an absolute bioavailability of 89% that is not markedly affected by concomitant intake of food. Meloxicam reaches maximum plasma concentration (Cmax) at 9-11 hours after a 30mg dose and 2.5-7 hours after a 15mg dose. Meloxicam is strongly bound to plasma proteins (99.5%). Meloxicam displays linear pharmacokinetics, with a half-life of 20-24 hours.[22]

During distribution, meloxicam readily penetrates the synovial fluid, reaching concentrations that are 45-57% of those in plasma.[22] Meloxicam concentrations in plasma and synovial fluids were measured in 42 patients with rheumatic disease after administration of a single oral dose of 15mg.[20] Meloxicam was found in synovial fluid 1 hour after administration and reached peak concentrations (320 µg/L. at approximately 6 hours, after which time a plateau was observed. After the distribution phase, the ratio of drug concentration in synovial fluid to that in plasma remained at a constant value of 0.47, and mean residence time and elimination half-life were similar in synovial fluid and plasma. Exposure (area under the concentration-time curve) to free drug was also similar in the two compartments.[20] Inflammatory status was found to affect the distribution of meloxicam into synovial fluid, shifting the synovial fluid : plasma ratio from 0.58 (acute inflammation) to 0.38 (no inflammation).[20]

The pharmacokinetic properties of meloxicam allow once-daily administration, which is an important factor in improving compliance, especially in the treatment of chronic rheumatic diseases, and contributing to the clinical benefits derived from uninterrupted therapy. It should be noted that, due to the long half-life of meloxicam, steady-state blood concentrations are not achieved before the third or fourth day after oral administration. Therefore, parenteral formulations of meloxicam have been developed in order to obtain a faster analgesic response in the treatment of syndromes involving acute pain.[22] Intramuscular meloxicam is rapidly absorbed, reaches Cmax at 1.5 hours after injection, and its absolute bioavailability is 100%. Notably, 90% of the Cmax is reached within 30-50 min of injection, and concentrations tend to remain stable for at least 5-6 hours (figure 2).[22] These data support the use of intramuscular meloxicam in patients with acute arthropathies, since it provides a fast relief of pain and inflammation.

Figure 2.

Concentration-time curves of oral (PO) and intramuscular (IM) meloxicam 15mg in volunteers. Values are means.[22]

Meloxicam undergoes extensive biotransformation in the liver (99%) and is eliminated through both the biliary and the urinary systems. The pharmacokinetic profile of meloxicam is not significantly altered in elderly patients or in those with mild renal impairment.[22] However, dosages not exceeding 7.5 mg/day are suggested in patients with renal impairment in order to avoid abnormal increases in plasma concentrations. The pharmacokinetic parameters of meloxicam were found to be similar in patients with hepatic cirrhosis and healthy volunteers.[22]

There is limited information on pharmacokinetic interactions between meloxicam and other drugs. Coadministration of antacids or cimetidine was not found to alter meloxicam pharmacokinetics, and the pharmacokinetics of digoxin, furosemide or methotrexate are not affected by concomitant administration of meloxicam.[22] Although NSAIDs are known to potentiate the effects of oral anticoagulants, no clinically significant prolongation of prothrombin time was observed after concomitant use of warfarin and meloxicam. However, since both drugs are metabolised by hepatic cyto-chrome P450 isoenzymes, it is advisable to monitor prothrombin time in patients treated with meloxicam and warfarin.[22]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....