Clinical pharmacokinetics of aztreonam.

Abstract

Aztreonam (azthreonam) is practically completely absorbed after intramuscular injection. After intravenous injection plasma concentrations follow a 2-compartment open model, with a t1/2 alpha of 0.20 hours. Volume of distribution at steady-state (Vdss) after intravenous or intramuscular injection is about 0.16 L/kg (0.42 L/kg for the free drug). After oral administration less than 1% of the drug is absorbed. Over a large dosage range plasma concentrations increase linearly with dose. No accumulation occurs after multiple dosing. Plasma binding in healthy subjects is about 56% and is not concentration dependent. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma concentration seems to depend mainly on the composition of the tissue. In inflamed meninges, penetration of aztreonam into CSF is more rapid than with uninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breast milk. The main route of elimination of aztreonam is by the kidney, partly by active tubular excretion, but this can be inhibited by probenecid. Extrarenal clearance is probably due to excretion by the liver. Metabolism occurs to a very limited extent. Total plasma clearance in healthy adults is about 140 ml/min (8.4 L/h) or 2 ml/min/kg (0.12 L/h/kg), and terminal half-life is 1.7 hours. In children clearance is similar to that in adults when expressed as a function of bodyweight, but in neonates, especially in low birthweight infants, it is less [about 1 ml/min/kg (0.06 L/h/kg)]. In various disease states the Vdss of aztreonam is not appreciably different from that found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)