Gentamicin dosing requirements in patients with acute pancreatitis

Increased endothelial permeability is postulated in patients with pancreatic inflammatory disease. As a result, a deficit in total circulating blood volume may occur as fluid is sequestered within the extravascular space. To counteract this fluid sequestration, exogenous fluid is administered, which results in expansion of total body water. The object of this study was to determine whether the fluid sequestration and potential total body water increase observed in patients with the diagnosis of pancreatitis affects the pharmacokinetics--and thus dosing requirements--of the water-soluble aminoglycoside gentamicin. Data collected from a clinical pharmacokinetic monitoring service were analyzed in 17 patients with primary diagnoses of acute pancreatitis and 17 closely matched controls. Volume of distribution corrected for total body weight (p = 0.029), volume of distribution corrected for ideal body weight (p = 0.031), and total body gentamicin clearance (p = 0.05) were determined to differ statistically in pancreatitis patients from those values calculated in control patients. Patients with pancreatic inflammatory disease, on the basis of these pharmacokinetic parameter estimates, were found to require approximately a 25% greater dose than controls in order to achieve therapeutic peak serum gentamicin concentrations.