Disposition of penicillin G after administration of benzathine penicillin G, or a combination of benzathine penicillin G and procaine penicillin G in cattle

Abstract

Summary Plasma concentration of penicillin G was evaluated in beef steers after administration of either a combination of benzathine penicillin G and procaine penicillin G in a 1:1 mixture at a dosage of 9,000 U/kg of body weight, im (n = 5), 24,000 U/kg, im (n = 5), or 8,800 U/kg, sc (n = 5), or benzathine penicillin G alone at a dosage of 12,000 U/kg, im (n = 7). Plasma concentration of penicillin G was measured by use of a high-performance liquid chromatography assay that had a limit of determination of 0.005 µg/ml. At a dosage for this combination of 9,000 U/kg im, and 8,800 U/kg, sc, which are approved label recommendations in Canada, and the United States, respectively, mean (± sem) peak plasma concentration was 0.58 (± 0.15) and 0.44 (± 0.02) µg/ml, respectively. Although plasma penicillin concentration was quantifiable for 7 days in the steers that received 9,000 U/kg, im, and for 4 days in the steers that received 8,800 U/kg, sc, the concentration was < 0.1 µg/ml in both groups after the first 12 hours. After administration of the combination at dosage of 24,000 U/kg, im, there was an initial peak plasma concentration at approximately 2 hours; thereafter, plasma concentration decreased slowly, with half-life of 58 hours. Although plasma penicillin G concentration was quantifiable for 12 days at this dosage, concentration was < 0.1 µg/ml after the first 48 hours. After the initial 48 hours, plasma concentration of penicillin was of similar magnitude and decreased at similar rate for the combination at dosage of 24,000 U/kg and for 12,000 U/kg of benzathine penicillin G alone. Most of the plasma penicillin G concentration in the first 24 hours after administration of a 1:1 combination of benzathine penicillin G and procaine penicillin G is attributable to absorption of procaine penicillin G. After the first 48 hours, most of the plasma drug concentration appeared to be produced by absorption of penicillin G from benzathine penicillin G. Absorption of benzathine penicillin G produces quantifiable plasma penicillin G concentrations for several days, but they are below the level of susceptibility for most bacteria.