[Pharmacokinetics of the antirheumatic lonazolac-Ca in humans]

The pharmacokinetics of the non-steroidal, antiinflammatory drug lonazolac-Ca in man was investigated. Lonazolac-Ca (Irritren, arthro akut, Argun-L, Argun-300) (single doses 200 mg or 300 mg) was administered both to healthy, young volunteers and to patients with renal impairment, to elderly and arthritic patients and to nursing women. Serum concentrations were measured for lonazolac and its main serum metabolite M1, and pharmacokinetic characteristics such as Cmax, AUC and t1/2 were calculated after both single and multiple oral doses of film-coated tablets of lonazolac-Ca. In addition also suppositories of lonazolac-Ca (single dose 400 mg) were tested after single and multiple administration. In a study in healthy, normal volunteers, total radioactivity in blood was followed after oral and i.v. administration of 14-C-lonazolac-Ca (-Na). Lonazolac and M1 generally showed a biphasic pattern of elimination, their terminal half-lives being both ca. 6 h in young volunteers. In elderly patients the terminal half-life was about twice as long. Nevertheless, no accumulation of lonazolac on multiple dosing was observed in either volunteers or patients due to the rapid alpha-phase. However, some accumulation occurred for the (pharmacologically inactive) M1 in elderly patients and in patients with renal impairment. Serum profiles were lower and flatter after administration of suppositories as compared to oral administration. Lonazolac concentrations in synovial fluid were about half of those in serum, no lonazolac could be found in breast milk although there was some transfer of M1.