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Prediction of the Concentration of Penicillins in Ascitic Fluid from Serum Kinetics and Protein Binding of the Antibiotics in Serum and Ascitic Fluid of Dogs

Dale N. Gerding, Lance R. Peterson, Janet K. Salomonson, Wendell H. Hall and Elizabeth A. Schierl
The Journal of Infectious Diseases
Vol. 138, No. 2 (Aug., 1978), pp. 166-173
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30081900
Page Count: 8
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Prediction of the Concentration of Penicillins in Ascitic Fluid from Serum Kinetics and Protein Binding of the Antibiotics in Serum and Ascitic Fluid of Dogs
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Abstract

Ascites was induced in dogs by partial ligation of the inferior vena cava. Concentrations of ampicillin, penicillin G, oxacillin, cloxacillin, dicloxacillin, nafcillin, and methicillin in ascitic fluid and serum were each determined in three animals. All antibiotics were administered intramuscularly in a dose of 15 mg/kg (dry weight) for both single-dose and multiple-dose (eight doses at 4-hr intervals) studies. Binding of antibiotics to serum and ascitic fluid proteins was measured by ultracentrifugation. After single doses the highly protein-bound drugs (oxacillin, cloxacillin, dicloxacillin, and nafcillin) had lower percentages of penetration (ratio of peak in ascitic fluid to that in serum, multiplied by 100) than did methicillin, ampicillin, and penicillin G, which have a lower degree of protein binding. The effect was partially overcome by repetitive doses, but five to six doses were usually required to reach equilibrium. In addition to protein binding, serum kinetics (particularly the log mean total concentration of drug in serum after multiple doses) were important determinants of antibiotic concentrations in ascitic fluid. The total antibiotic concentration in ascitic fluid at equilibrium can be accurately calculated from the log mean serum concentration and the percentages of protein binding in serum and ascitic fluid.

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