The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of > 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 microgram/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study. Flunixin concentrations necessary to induce therapeutic effects in cattle are unknown. Results of our study indicate that administration of 1.1 mg/kg doses of flunixin meglumine at 8-hour intervals would produce plasma concentrations similar to those demonstrated to be effective clinically in treatment of equine musculoskeletal disorders and colic.

The purpose of this project was to study the effect of superalimentation in lactating sows through permanent, surgically placed, gastric cannulas. A surgical technique was developed to install gastric cannulas into pregnant sows to allow superalimentation by introducing feed through the cannula. After induction of general anesthesia, a flexible, T-shaped cannula (22 mm outside diameter) was surgically placed in the dorsal portion of the greater curvature of the stomach and exteriorized through the tenth intercostal space approximately 30 cm left of the dorsal midline. Cannulas were installed on day 85 5 days of gestation. Anesthesia, surgical procedures, and the subsequent presence of the cannula did not affect the size ornumber of live pigs at birth. In addition, the prevalence of stillbirths and mummified fetuses was not significantly different than that of noncannulated sows. The gastric cannulas did not affect lactation performance, as litter size and weight were unaffected when compared with that in noncannulated controls. Postmortem examination of euthanatized sows revealed adhesions of the gastric wall to the abdominal wall, thus eliminating the possibility of leakage of the gastric contents into the peritoneum. Detrimental effects of the cannulas on gastric function or capacity were not detected, and cannulas could be maintained through multiple parities.

The effect Of bovine mammary secretion during the nonlactating period and of antibiotic preparations on bovine polymorphonuclear neutrophil (PMN) phagocytic function and morphology were evaluated in a series of in vitro multifactorial experiments. Benzathine cloxacillin (CL), benzathine cephapirin (CE), sodium novobiocin (NO), and a combination of dihydrostreptomycin with procaine penicillin G (DP) were prepared in the presence and absence of a peanut oil aluminum monostearate vehicle. The PMN were isolated from bovine blood, and the effect of each antibiotic preparation on PMN function and morphology was evaluated in a buffer, fat, skim, and a combination of fat with skim from bovine mammary secretion during the nonlactating period. The fat and skim were diluted with buffer to approximate their concentration in mammary secretion. Phagocytic functions of PMN were monitored by fluorescent microscopy, which made it possible to estimate both ingestion and intracellular killing of bacteria by PMN. Changes in PMN morphology were monitored by transmission electron microscopy. The ability of PMN to ingest and kill Staphylococcus aureus ATCC 25923 was significantly decreased by fat, skim, CL, CE, NO, and DP. Effects of some antibiotics on ingestion and killing of bacteria by PMN were influenced by the addition of vehicle and by interactions with mammary secretion. Neutrophil morphology was altered by fat, skim, CL, CE, NO, and DP. The detrimental effects of CL, CE, NO, and DP on PMN morphology were influenced (some significantly) by the presence of vehicle and interactions with mammary secretion. There were significant correlations among secretion- and antibiotic-induced changes in PMN ingestion of bacteria, PMN killing of bacteria, and PMN morphology.

The effects of 2 antibiotic preparations administered intramammarily on phagocyte recruitment, function, an morphology were evaluated at the beginning of the nonlactating period. Twelve cows with no clinical or micro biologic evidence of mastitis were assigned to 1 of 2 treatment groups. At the end of lactation, 1 of the antibiotic preparations was infused in a fore- and hind quarter of each cow; the remaining quarters were untreated controls. One group was given benzathine cephapirin; the second group was given sodium novobiocin. Secretion samples were collected from 1 treated and 1 control quarter at 16 hours, and from the remaining 2 quarters at 64 hours after treatment. Total and differential somatic cell counts were determined, and morphology of mammary polymorphonuclear neutrophils (PMN) and macrophages was observed by transmission electron microscopy. In vitro ingestion and killing of Staphylococcus aureus by mammary PMN and macrophages were assessed by fluorescent microscopy, using acridine orange stain. Cells resident in a fixed volume of secretion were incubated with a known concentration of S aureus. Total cell and PMN concentrations were higher in treated than in control quarters. Neutrophils were the predominant cell type in both treated and control quarters over the sampling period. As measured in this study, in vitro ingestion and killing of S aureus by individual PMN from treated quarters was reduced. Antibiotic treatment also increased the proportion of morphologically abnormal phagocytes. There were significant correlations among PMN ingestion, killing, and morphology. However, increased PMN concentrations tended to compensate for the reduced phagocytic function of individual cells. Therefore, efficacy of antibiotic treatment of nonlactating cows may depend, at least in part, on increased PMN concentration, which may tend to compensate for reduced phagocytic function. Compared with PMN, macrophages appeared to have only a minor role in phagocytosis of bacteria.