[Clinical pharmacokinetics of azlocillin]

Abstract

The pharmacokinetics of azlocillin have been studied in healthy subjects and in patients, in children and in adults, using different doses, either single or repeated. Following intravenous injection of doses ranging from 1 to 5 g, plasma concentrations increase in relation to dosage. Maximum concentrations at the end of an injection or infusion average 100-200 micrograms/ml with 1 g and 400-500 micrograms/ml with 5 g. Azlocillin has a low degree of plasma protein binding: 30% to 40% depending on concentrations. Its volume of distribution is approximately 0.2 l/kg. Tissue distribution has been studied by various authors: with a 2 to 5 g dose, therapeutically active concentrations have been found in a variety of tissues, including bronchial secretions, bone, etc. Azlocillin crosses the placenta; the ratio of maternal to foetal plasma concentrations is 0.50. Azlocillin undergoes little metabolic degradation and its metabolites (penicilloates) amount to less than 15% of the dose administered. Most of the drug is excreted by the kidneys, 50% to 70% of the dose injected being recovered in the 24 h urines; the remainder is excreted in the bile, and biliary concentrations may be as high as 15-fold the corresponding plasma concentrations. Azlocillin is rapidly cleared. Its plasma half-life varies from 45 to 75 min according to different authors. The fact that it increases slightly with dosage suggests the kinetics of the drug might be dose-dependent. In view of the intervals between doses, this is certainly not of therapeutic importance. Total and renal clearance values are 150-200 ml/min and 100-140 ml/min respectively. In patients with renal impairment azlocillin is eliminated more slowly, with a half-life of up to 6-10 h when creatinine clearance is below 5 ml/min. The reduced urinary excretion may partly be compensated for by increased biliary excretion. The proportion of drug removed by haemodialysis is 40-50%. Azlocillin excretion is slowed down in children under 3 months of age, with half-lives of 4.5 h, 3.0 h and 2.0 h respectively in prematures, neonates and infants.