[Human pharmacokinetics of different i.v. doses of azapropazone (HPLC-determination) (author's transl)]

The pharmacokinetic profile of azapropazone (Prolixan), sodium salt of 5-dimethylamino-9,5-dimethylamine-9-methyl-5-propyl-1H-pyrazolol[1,2-a][1,2,4]benzotriazine-1,3(2H)-dione, was established. Six healthy, adult volunteers received a single dose of either 600 mg or 1200 mg azapropazone as sodium salt intravenously. The drug was selectively separated from its metabolites and other plasmatic compounds and it was quantified by measurement of extinction at 254 nm. The kinetic parameters of azapropazone were independent of the applied dose (600 mg and 1200 mg): Biological half-life (t0.5): 16.8 +/- 2.95 h and 17.2 +/- 3.0 h; Total clearance (Cltot): 10.2 +/- 2.1 ml min-1 (both doses); Central volume of distribution (Vc): 3.7 +/- 0.71 and 3.9 +/- 0.91; Apparent volume of distribution (Vd): 12.5 +/- 2.91 and 14.4 +/- 2.41. Initial serum concentrations were 170 +/- 41.5 micrograms ml-1 and 326.3 +/- 84.5 micrograms ml-1, determined by extrapolation (C0 at time t0). The areas under the plasma concentration curves (AUC0 infinity) were calculated to amount 1052.5 +/- 217.4 micrograms ml-1h-1 and 2078.4 +/- 515.9 micrograms ml-1h-1. Three rate constants associated with the elimination of the drug could be calculated.