Clinical Pharmacokinetics of Aztreonam: An Update

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Plasma concentrations of aztreonam follow a 2-compartment open model with a distribution half-life of 0.20 hours after intravenous injection. The volume of distribution at steady-state (Vss) after intravenous and intramuscular injection is about 0.16 L/kg (0.42 L/kg for free drug). After intramuscular injection, absorption is almost complete. Absorption after intraperitoneal administration in patients with peritonitis is 92%. Over a large dosage range, plasma concentrations increase dose proportionally. In healthy individuals, about 56% of the drug is plasma 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 cerebrospinal fluid (CSF) more rapidly in patients with inflamed meninges than in those with noninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breastmilk.

Aztreonam is predominantly eliminated by the kidney, partly by active tubular excretion. Extrarenal clearance appears to be through hepatic excretion. Metabolism occurs to a very limited extent. Total plasma clearance (CLP) in healthy adults 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 as a function of bodyweight. However, in neonates, especially in low birthweight infants, CLP is lower.

In various disease states, the VSS of aztreonam is not appreciably different from that found in healthy individuals. However, patients with low serum albumin levels (e.g. burn patients, critically ill patients and those with cirrhosis of the liver) 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 peritoneal dialysis has little effect on aztreonam clearance.

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