CLINICAL PHARMACOKINETICS OF AZTREONAM - AN UPDATE

Plasma concentrations of aztreonam follow a 2-compartment open model w ith a distribution half-life of 0.20 hours after intravenous injection . The volume of distribution at steady-state (V-ss) after intravenous and intramuscular injection is about 0.16 L/kg (0.42 L/kg for free dru g). After intramuscular injection, absorption is almost complete. Abso rption after intraperitoneal administration in patients with peritonit is is 92%. Over a large dosage range, plasma concentrations increase d ose proportionally. In healthy individuals, about 56% of the drug is p lasma protein bound. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma aztreonam concentration seems to depend mainly on tissue composition. Aztreonam penetrates into cerebr ospinal fluid (CSF) more rapidly in patients with inflamed meninges th an in those with noninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breastmilk. Aztreonam is predominantly e liminated by the kidney, partly by active tubular excretion. Extrarena l clearance appears to be through hepatic excretion. Metabolism occurs to a very limited extent. Total plasma clearance (CLp) in healthy adu lts is about 5.6 L/h and the terminal elimination half-life is 1.7 to 2.0 hours. CLp is similar in both children and adults when expressed a s a function of bodyweight. However, in neonates, especially in low bi rthweight infants, CLp is lower. In various disease states, the V-ss o f aztreonam is not appreciably different from that found in healthy in dividuals. However, patients with low serum albumin levels (e.g. burn patients, critically ill patients and those with cirrhosis of the live r) generally have an increased volume of distribution. The elimination half-life of the drug is dependent on renal function. For example, in anuric patients the elimination half-life is 8 to 10 hours. Aztreonam removal from plasma by haemodialysis is modestly effective, but perit oneal dialysis has little effect on aztreonam clearance.