Pharmacokinetics of azlocillin after discontinuous intravenous administration of high dose

Azlocillin, an acylureido-penicillin, is often used in severe, and sometimes in life-threatening infections because of its good therapeutic effect, even against bacteria resistant to many other agents. In these patients sometimes doses of 10 g may be administered in order to improve therapeutic efficacy. In this study the serum concentrations and urinary excretion of azlocillin were investigated in 2 volunteers and 11 patients after the intravenous injection (5 min) of 2 g followed by intravenous infusion of 8 g over 4 h. The serum concentrations increased during infusion in volunteers and patients from a median value of 180 mg/l up to 317 mg/l. After the end of infusion the median concentrations fell through 94 mg/l at 2 h, and 43 mg/l at 4 h to 11 mg/l at 6 h. The median cumulative urinary excretions in patients were 2.50 g up to 4 h, 4.51 g up to 8 h, 4.89 g up to 12 h, and 5.43 g up to 24 h after the end of infusion. The median plasma half-life calculated from the last five serum concentrations (6-10 h after start of administration) was 100 min (range 60-180 min). The study showed that using this dose and mode of administration high serum concentrations can be maintained over many hours, which would be sufficient to treat life-threatening or difficult infections. The dose interval would have to be 12 h. The local and systemic tolerability was good, as shown by the laboratory parameters measured.