PHARMACOKINETICS AND TOLERABILITY OF MELOXICAM AFTER IM ADMINISTRATION

1 The pharmacokinetics and tolerability of a new nonsteroidal anti-inf lammatory drug (NSAID), meloxicam, administered i.m., were investigate d in two studies conducted in healthy male volunteers. Study 1 was an open, placebo-controlled design in which 32 volunteers were randomized to a single ascending i.m. dose of meloxicam (5, 10, 20, and 30 mg) o r placebo. Study 2 had an open, randomized two way crossover design in which 12 volunteers received single i.m. and i.v. doses of meloxicam (15 mg). 2 Meloxicam showed an excellent tolerability in both studies. No effect was seen on serum creatinphosphokinase (CK, the isoenzyme o f the skeletal muscle enzyme, CK-MM, was determined). 3 Following i.m. administration meloxicam was rapidly and completely absorbed (mean ab solute bioavailability 102 %). Dose-proportionality was demonstrated w ith respect to C-max (maximum plasma concentration) and AUC (extrapola ted area under the plasma concentration-time curve from zero time to i nfinity) over a range of 5-30 mg. 4 Intravenous administration of melo xicam (15 mg) resulted in higher initial plasma concentrations (C-3min , i.e. concentration in plasma 3 min after start of injection = 2.99 /- 0.75 mu g(.)ml(-1)) than after i.m. injection (C-max: 1.62 +/- 0.20 mg ml(-1)). All other pharmacokinetic parameters were similar for bot h routes of administration (apparent elimination half-life = 15-22 h; plasma clearance = 7-9 ml min(-1)). 5 In conclusion, the excellent tol erability of i.m. meloxicam together with its rapid and complete absor ption may provide an alternative to oral administration of this drug.