Pharmacokinetic profile of imidazole 2-hydroxybenzoate, a novel nonsteroidal antiinflammatory agent.
Imidazole 2-hydroxybenzoate is a novel nonsteroidal antiinflammatory agent which clinico-pharmacologically and pharmacokinetically has to be understood as imidazole and salicylic acid. The pharmacokinetic profile of both components after single and multiple oral (tablets, drops), and topical administration (gel 5%)--the latter in a pilot study--was evaluated as well as protein-binding, relative bioavailability and the metabolic pattern. Absorption and elimination of the two compounds were fast. All essential pharmacokinetic and bioavailability parameters seem to be in a good agreement with data published in the literature and an accumulation tendency was not observed. The t1/2 beta for imidazole (oral administration) was determined for a single dose at 2.98 +/- 1.13 h, for a multiple dose (last dose) at 1.86 +/- 0.78 h; for salicylic acid the t1/2 beta for a single dose was determined at 6.46 +/- 3.79 h and for a multiple dose (last dose) at 6.40 +/- 3.36 h. The protein-binding of imidazole was in the range of 5-15% and of salicylic acid of about 80-85%. The relative bioavailability was calculated for imidazole (single dose) at 138% and for multiple dosing (last dose) at 113%; for salicylic acid the values for single dose were 148% and for multiple dosing (last dose) 128%. The tolerability was altogether good and no adverse reactions could be observed. The topical administration (pilot study) with gel 5% did not show any systemic effects or adverse reactions. The local tolerability was very good. Statistically, there were only slight differences between tablets and drops overall since only one p-value was less than 0.01. According to the small sum of squared residuals, the NONLIN-program performed an excellent fitting of the data to the model equation.
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D011485:Protein Binding; D012459:Salicylates / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D012996:Solutions; D013607:Tablets
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D012459:Salicylates; D012709:Serum Albumin; D012996:Solutions; D013607:Tablets; C043292:imidazole-2-hydroxybenzoate