Evaluation of route and frequency of administration of three antimicrobial drugs in cattle.

This study in six cows compared serum concentrations of trimethoprim and sulphadoxine (16 mg/kg body weight (BW)) after once daily and twice daily administration, and of procaine penicillin G (20,000 IU/kg BW) after subcutaneous (SQ) and intramuscular (IM) administration, and evaluated postmortem tissue concentrations of penicillin following SQ treatment. Trimethoprim and penicillin were measured microbiologically, and sulphadoxine colorimetrically. Using minimum inhibitory concentrations (MIC), trimethoprim reached serum concentrations above 0.5 mug/mL from 15 minutes to 120 minutes, and sulphadoxine exceeded 9.5 mug/mL from 10 minutes to 12 hours, after administration. At 24 hours after treatment, both had declined to below the MIC of most organisms. A second treatment at 12 hours maintained concentrations of sulphadoxine above 9.5 mug/mL for a further 24 hours. For penicillin administered IM and SQ, concentrations that peaked at 0.88 mug/mL would inhibit most common grampositive bacteria for the entire 24 hour period and fastidious gram-negative organisms from 90 minutes to 12 hours after SQ treatment, but for virtually the entire period after IM administration. Mean +/- SD concentrations (mug/mL) of penicillin at euthanasia, five days after the last SQ administration, were 1.15 +/- 1.27 (injection site), 1.00 +/- 0.80 (liver), 0.90 +/- 0.58 (renal cortex), 0,58 +/- 0.17 (renal medulla), 0.13 +/- 0.11 (diaphragm), 0.10 +/- 0.08 (gluteal muscle), and 0.06 +/- 0.04 (fat). Therefore, except for the most sensitive organisms, twice daily injection of trimethoprim/sulphadoxine (16 mg/kg BW) may be required. Penicillin G administered SQ at 20,000 IU/kg BW should provide effective serum levels for as long as IM administration against gram-positive organisms, but for only about half as long against gram-negative bacteria. The label withdrawal time of five days cannot be used when penicillin is given SQ at 20,000 IU/kg BW for three days.