Pharmacokinetics of endotoxin in a rhesus macaque septic shock model

Using a prospective, randomized, controlled study, we tested the hypothesis that the initial administered dose of endotoxin determines its pharmacokinetics in a rhesus macaque septic shock model. Twelve adult male rhesus macaques, weighing 6 to 10 kg, were equally divided into two groups. The first group received a 20 mg/kg intravenous bolus of the gram-negative endotoxin. The second group received a bolus comparable to the concentration of endotoxin found in the plasma of the first group, 12 hr postendotoxin injection. Both groups were monitored for 12 hr and sacrificed. Plasma endotoxin concentrations were measured using the limulus amebocyte lysate assay and a pharmacokinetic model was applied to the concentration curves. Results of the pharmacokinetic evaluation revealed differences in half-life, clearance, and total apparent volume of distribution between the two groups of animals, suggesting that the changes in these parameters may have a biphasic pattern and may be related to the initial dose of endotoxin injected.