Concentrations of penicillin-G in serum were determined after single intravenous doses of potassium penicillin-G (10 mg/kg body wt) to ewes and cows in late pregnancy and in early lactation. Penicillin-G in serum was analysed by a microbiological method and pharmacokinetic parameters were calculated by model-independent methods. Serum concentrations were lower in early lactation than in late pregnancy in both ewes and cows. The differences were statistically significant at most sampling times in ewes but only during the first hour in cows. Weight corrected values of clearance and volume of distribution were significantly higher in early lactation than in late pregnancy in both ewes and cows. Mean residence time and elimination-half life were shorter in lactating than in pregnant ewes, however for the latter parameter the difference was not statistically significant. Neither of these parameters changed in cows. It is concluded that in both ewes and cows pharmacokinetic parameters of penicillin-G are altered from late pregnancy to early lactation but that these changes have little practical impact and do not call for a revised dosage regime of the studied drug.

Tissue cages implanted subcutaneously in calves were infected with Escherichia coli. Twenty-four hours later, the calves were treated either with single doses of 2.5 + 12.5 or 5 + 25 mg/kg trimethoprim (TMP) + sulfadoxine (SDX) or with five doses of 7.5 + 37.5 mg/kg TMP + SDX at 12-h intervals. In addition, one cage in each of three calves in the highest dose group was infected 3 h after initiation of treatment. Untreated calves were kept as controls. Concentrations of TMP and SDX in plasma and tissue cage fluid (TCF) and counts of viable bacteria in TCF were determined. In the highest dose group, concentrations of TMP in TCF remained above the minimum inhibitory concentration of the test strain for 94-101 h and peak to minimum inhibitory concentration (MIC) ratio was close to 10. In spite of this, an effect of treatment was noted only in cages infected after initiation of treatment. In vitro studies and analysis of thymidine content in serum and TCF from calves suggest that levels of thymidine in TCF are high enough to antagonize the antibacterial effect of TMP. The results indicate that soft tissue infections in secluded infection sites of calves are refractory to treatment with TMP + SDX.

Concentrations of oxytetracycline (OTC) in serum and tissue-cage fluid (TCF) from subcutaneous tissue-cages were determined after single and repeated intravenous and intramuscular doses of 10 mg/kg to calves. Intravenous administration resulted in higher levels, and greater area under curve (AUC) in TCF, than did intramuscular administration. However, the penetration measured as the ratio of AUC in TCF to AUC in serum was equal, and therefore independent of the route of administration. A linear relationship between AUC in serum and AUC in TCF could be demonstrated. Half-lives of OTC in serum were 4.9 +/- 3.1 h after intravenous, and 6.1 +/- 2.0 h after intramuscular administration. In TCF the half-lives were 21.5 +/- 4.4 h and 24.5 +/- 11.5 h after intravenous and intramuscular administration, respectively. Repeated dosing resulted in accumulation of OTC in TCF. Lesser accumulation in older cages indicated altered characteristics of the cages with the passage of time. In serum, no substantial accumulation was seen after repeated i.v. dosing until the dosing interval was shortened to 6 h.

Drug concentrations in serum, synovial fluid and tissue cage fluid (TCF) in calves were measured after single i.m. doses of oxytetracycline hydrochloride (OTC), procaine penicillin G (PPG) and potassium penicillin G (KPG) and single i.v. doses of sulphadimidine (SDM) and OTC. For all drugs, concentration-time curves in serum and synovial fluid were not identical but they had similar profiles, with peak levels occurring at about the same time. Concurrent concentrations were lower in synovial fluid than in serum. For each drug, elimination half-lives from synovial fluid and from serum were similar, except for penicillin G after KPG administration which had a significantly longer half-life from synovial fluid than from serum (P less than 0.05). Of the two penicillin G preparations, PPG gave a significantly higher synovial fluid:serum area under curve (AUC) ratio than did KPG; 0.76 +/- 0.10 and 0.54 +/- 0.12, respectively (P less than 0.05). For OTC, the synovial fluid:serum AUC-ratio was 0.33 +/- 0.12 after i.m. and 0.34 +/- 0.08 after i.v. administration. Drug concentration-time curves of TCF had different profiles compared with serum, with relatively low and delayed peak levels and slow elimination from TCF. TCF:serum AUC-ratios did not differ significantly for i.m. and i.v. administration of OTC; 0.10 +/- 0.10 and 0.19 +/- 0.03 respectively (P greater than 0.05). Potassium penicillin G (KPG), however, gave a significantly higher TCF:serum AUC-ratio than PPG; 0.55 +/- 0.21 and 0.19 +/- 0.07, respectively (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of one single therapeutic dose of flumethasone (0.5 mg/100 kgb.w.) on insulin sensitivity was studied in calves. Hyperinsulinemic, euglycemic clamp tests were performed before and after flumethasone treatment. At 24 h after treatment, insulin-dependent glucose utilization was reduced by 74% (p < 0.005). No significant changes occurred 72 h post-treatment.