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RESEARCH PRODUCT

Alteration of vancomycin pharmacokinetics during cardiopulmonary bypass in patients undergoing cardiac surgery.

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The alteration of vancomycin pharmacokinetics during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery was studied. Eighteen patients were enrolled in the study. Vancomycin (1 g) was intravenously infused one to two hours before surgery. Blood samples were taken before, during, and after CPB. Serum drug concentrations were determined by an automated fluorescence polarization immunoassay and adjusted, with a bayesian analysis, to a bi-compartmental model implemented in a pharmacokinetic system program. Serum creatinine, hematocrit, and plasma proteins were also measured before, during, and after CPB. During CPB, serum creatinine, hematocrit, and plasma protein values all decreased significantly (p < 0.05). Serum vancomycin concentration also diminished abruptly with CPB (7.04 micrograms/mL; 95% confidence interval, 5.70-8.38 micrograms/mL) but increased moderately during the next 30 minutes, probably attributable to redistribution into plasma from tissue stores. Vancomycin's apparent volume of distribution showed an important increase during CPB (58.8%) (p < 0.0005), and its systemic clearance also increased significantly after CPB (19.7%) (p < 0.0005). The decrease in serum vancomycin concentration seems mediated by the hemodilution associated with the pump prime volume. Vancomycin's mean +/- S.D. nadir serum concentration before the next dose was 7.13 +/- 2.1 micrograms/mL. In patients undergoing cardiac surgery and treated prophylactically with a 1-g preoperative i.v. dose of vancomycin, the onset of CPB was associated with a drop in serum vancomycin concentration.