Pharmacokinetics of azlocillin in normal renal function: single and repetitive dosing studies

Systemic and urinary pharmacokinetic studies of the disposition of azlocillin were performed in seven male and six female healthy volunteers. Four separate studies identified the kinetics of the drug following a single 2, 3 or 4 g administration and during the repetitive administrations of 3 g of the drug over a five-day period. Peak plasma concentrations were 174 +/- 19 mg/l, 214 +/- 17 mg/l and 286 +/- 11 mg/l in the 2, 3 and 4 g single dose studies respectively. Trough values at 4 h post-dosing were 6 +/- 1 mg/l, 10 +/- 1 mg/l and 26 +/- 3 mg/l respectively. The plasma half-life of azlocillin was approximately 60 min. A dose-dependent phenomenon was observed. This was characterized by a slight but significant progressive increase in the plasma half-life of the drug as increasing amounts of drug were given and as the same amount was given repeatedly. No significant systemic accumulation of azlocillin was noted during the repetitive dosing study. The urinary excretion of the compound was prompt with most of the bioactive drug being eliminated in the first 4-6 h following dosing. The apparent volume of distribution of azlocillin was slightly greater than the extracellular fluid compartment. For the therapy of systemic infections in adults with normal renal function a 4 h or 6 h dosing cycle would be appropriate.