Zidometacin: pharmacokinetic study on oral absorption

Zidometacin is a new nonsteroidal antiinflammatory agent structurally related to indomethacin. Pharmacological studies show its favourable activity/ulcerogenicity ratio in comparison to indomethacin. Preliminary clinical data indicate a good analgesic effect after a single dose and an improvement of functional conditions of the joint after short-term therapy. Pharmacokinetic parameters and bioavailability of the drug were evaluated in the present study after the administration of a single oral dose. Nine healthy volunteers without impairment of hepatic and renal function were selected. According to a 3 X 3 replicated latin square they received a 100 mg capsule, a 200 mg capsule and a 100 mg solution (sodium salt). After various time intervals, blood samples and urines were collected. Plasma and urine levels were evaluated by means of a specific high-performance liquid chromatography method. No difference between plasma levels of capsules (100 mg) and solution (100 mg) was observed. Capsules showed a dose/level relationship between 100 mg and 200 mg. Mean half-lives (+/- s.d.) of capsules (100 and 200 mg) and solution were respectively 3.5 +/- 2.33, 2.8 +/- 1.22, 4.4 +/- 2.96 h. The 0-48 h recovery of total zidometacin (free + conjugated) was 27.4% (100 mg capsule), 20.7% (200 mg capsule) and 24.6% (solution). Only a small amount of zidometacin was excreted unchanged. The drug is well absorbed and its bioavailability appears satisfactory.