Review of the pharmacokinetics and dose dependency of azlocillin in normal subjects and patients with renal insufficiency.

Cross-over studies on volunteers with several doses of azlocillin ranging from 1.0 to 5.0 g have shown that azlocillin is subject to dose dependent pharmacokinetics, the area under the serum curve becoming larger than expected as doses increase. There was also a tendency towards longer serum half-life values and excretion of more unchanged compound as the doses increase. The serum half-life varied between 0.9 h after 1.0 g increasing to 1.5 h after intravenous doses of 5.0 g given to adults. In neonates, values around 2.6 h have been observed, and they were slightly longer in premature babies at approximately twice the value in adults receiving similar doses per kg body weight. In normal adults protein binding lies between 35 and 40% for therapeutic concentrations. Approximately 60-75% of the dose appears as unchanged azlocillin in the urine, increasing with higher doses. Reduced renal function lowers urinary excretion, but concentrations are always above the break point for sensitivity of 32 mg/l in patients with creatinine clearances above 10 ml/min. In anephric subjects T1/2 of 2.5-6 h is observed. Dosage modifications only to one-third of normal are needed for a renal clearance of 10-25 ml/min. The concentrations of active compound are high in the bile in subjects with normal liver function.