Pharmacokinetic variables of skeletal muscle creatine kinase (CK) activity after IV administration of a muscle extract; CK bioavailability after IM administration of the muscle extract; and effect of IM administration of saline solution, to appreciate the possible release of CK consecutive to muscle puncture, were determined in 6 cows. A general equation for the quantitative estimation of skeletal muscle damage also was derived. Administration of saline solution IM had no effect on plasma CK activity (ANOVA, P > 0.05) in any of the cows. After IV administration of the muscle extract (150 U/kg of body weight), mean volume of the central compartment, plasma half-life, and plasma clearance of CK were 0.027 +/- 0.007 L/kg, 520 +/- 109 minutes, and 6.43 +/- 2.29 ml/kg/h, respectively. After IM administration (150 U/kg), mean bioavailability of CK was 51 +/- 17% and maximal plasma CK activity (500 +/- 97 U/L) was observed at 454 +/- 131 minutes. The rate of CK activity entry into plasma was determined by use of deconvolution analysis. Two peaks were observed; the first appeared before the 30th minute after IM administration, and the second appeared at 3.3 +/- 1.1 hours. Amplitudes were 6.31 +/- 4.45 and 6.57 +/- 3.08 U/kg/h, for the first and the second peaks, respectively. The quantity of CK liberated from control muscle was 0.69 +/- 0.12 U/kg/h, corresponding to a normal daily catabolism of 5.8 +/- 1.0 mg of muscle/kg. From these results, the following equation can be proposed to determine the corresponding mean equivalent of destroyed muscle (Qmuscle, test article) after IM administration of a test article: Qmuscle, test article (g/kg) = 4.41 X 10(-6) AUC (U/h/L), with AUC being the CK plasma activity area under the curve.

Persistence of the vaccine RH strain of Toxoplasma gondii was studied by bioassay and histologically in 14 pigs. Pigs were euthanatized 2, 4, 7, 8, 14, 15, 21, 29, 36, 42, 52, 57, and 76 days after IM inoculation with 100,000 T gondii tachyzoites. Viable T gondii tachyzoites derived from the RH strain were isolated by bioassay in mice inoculated with tissues of pigs euthanatized up to 14 days after vaccination. Except for fever, pigs vaccinated IM with the RH strain remained clinically normal. Two other pigs inoculated IV with 100,000 T gondii tachyzoites of the RH strain became ill, and 1 pig was comatose by 4 days after inoculation. These findings indicate that route of inoculation may influence the response of pigs to T gondii. To evaluate protective immunity in pigs vaccinated with the RH strain, 16 age-matched pigs were allotted to 4 groups (A-D) of 4 pigs each. Eight pigs (groups A and C) were vaccinated IM with 100,000 RH strain tachyzoites and 8 pigs (groups B and D) were nonvaccinated controls. Pigs of groups A and C were challenge-inoculated orally with a lethal dose of T gondii oocysts (100,000 oocysts) 81 days after vaccination, pigs of groups B and D were inoculated similarly 220 days after vaccination. The concentration of T gondii at 3 days after challenge inoculation of pigs vaccinated 81 days earlier was reduced 100,000-fold in mesenteric lymph nodes, compared with that in a nonvaccinated pig euthanatized at 3 days after challenge inoculation. Another nonvaccinated pig became comatose and had to be euthanatized at 7 days after challenge inoculation, numerous tachyzoites were in its mesenteric lymph nodes, intestines, and liver. The vaccinated pigs generally remained clinically after challenge inoculation with oocysts. Toxoplasma gondii was not isolated by bioassays from tissues of 5 of 8 vaccinated pigs, but was recovered from all nonvaccinated pigs. Results indicate that protective immunity persisted in pigs for at least 7 months after vaccination with the nonpersistent RH strain of T gondii.

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 micrograms/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) micrograms/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 micrograms/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 micrograms/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.

Effects of dietary aflatoxin (AF) and supplemental vitamin E (d-alpha-tocopherol) were evaluated in growing crossbred pigs. Nine barrows (3 replicates of 3 each, mean body weight, 14.0 kg) per group were assigned to 1 of 4 treatment groups (for a total of 36 barrows): 0 IU of supplemental vitamin E and 0 mg of AF/kg of feed (control); 2,400 IU of vitamin E divided into equal doses and administered IM on days 1 and 16; 2.5 mg of AF/kg of feed; or 2.5 mg of AF/kg of feed plus 2,400 IU of vitamin E administered similarly to treatment 2. Barrows were administered their respective treatment for 32 days. Evaluations were made for group production performance and for serum biochemical, immunologic, hematologic, pathologic, serum and tissue tocopherol, and serum retinol variables. Body weight was reduced by AF-alone and AF plus vitamin E treatments, compared with control and vitamin E-alone treatments. Liver weight was increased for the AF alone-treated and the AF plus vitamin E-treated barrows, compared with control barrows. The AF alone-treated barrows had alterations in: serum values of alkaline phosphatase, gamma-glutamyltransferase, albumin, glucose, phosphorus, calcium, cholesterol, total iron, unsaturated iron-binding capacity, total iron-binding capacity, and urea nitrogen; RBC numbers, hematocrit, hemoglobin concentration, and prothrombin time; and mitogen-induced lymphoblastogenic responses. With the exception of some slight ameliorating effects on hematologic measurements, supplemental treatment with vitamin E did not prove beneficial against the toxicosis-associated AF treatment. The AF alone-treated barrows had decreased serum tocopherol and retinol concentrations, compared with control and pretest values, and decreased tocopherol concentration in cardiac tissue. High parenterally administered doses of vitamin E did not have sparing effect on Af-induced reductions of serum tocopherol or retinol concentration; however, compared with pretest values, serum tocopherol concentration was increased by vitamin E-alone treatment. Tocopherol concentration in cardiac tissue of the AF plus vitamin E-treated barrows was increased over that of the AF alone-treated barrows, indicating an ameliorating effect on AF-induced tissue concentrations reductions. These data indicate that vitamin E may not have a sparing effect on AF-induced toxicosis and that AF may reduce serum retinol and serum and tissue tocopherol concentrations.