MELOXICAM - PHARMACOKINETICS AND METABOLIC PATTERN AFTER INTRAVENOUS-INFUSION AND ORAL-ADMINISTRATION TO HEALTHY-SUBJECTS

Meloxicam l)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide] is a new nonsteroidal antiinflammatory drug belonging to the enolic acid group. In a crossover study, 30 mg C-14-labeled meloxicam was administered t o four male healthy volunteers as a short-term infusion and as an oral solution, The objectives of the study were to determine the mode of e limination, the excretion balance, the in vivo binding characteristics to serum proteins, and to investigate the metabolic pattern in plasma , urine, and feces, A comparison of plasma concentration measurements of unchanged drug by a specific HPLC assay and total radioactivity by liquid scintillation counting revealed a very close conformity, Over 9 0% of the plasma radioactivity was represented by unchanged drug, Its terminal and dominant half-life of elimination from plasma, as determi ned from plasma and urinary data in this study, ranged from 12 to 17 h r in the volunteers, The serum protein binding of the radioactivity fr om in vivo samples was very high (99.1-99.7%), The excretion balance w as complete after 6 days. Average urinary excretion of(14)C-radioactiv ity accounted for 43% of the dose, with the remainder appearing with t he feces. Meloxicam was extensively metabolized, with only traces of t he drug appearing unchanged in urine and feces. The main metabolites w ere formed by hydroxylation and further oxidation of the methyl group of the thiazolyl moiety, In addition, two further metabolites were fou nd, particularly in urine, Altogether, >95% of the dose excreted could be accounted for by the metabolites identified or the parent compound itself.