Pharmacokinetic study of sulfadimethoxine depletion in suckling and growing pigs.

Sulfadimethoxine was administered (IV) to suckling pigs (1 to 2 weeks old) and to growing pigs (11 to 12 weeks old) at a dosage of 55 mg/kg of body weight (single dose). Blood samples were collected over a 48-hour period, and the animals euthanatized were used for measurements of plasma and tissue concentrations of the drug. The blood data were described, using a one-compartment pharmacokinetic model. The blood concentration curves for the two groups of pigs had a consistent depletion pattern with greater than therapeutic concentrations (50 micrograms/ml) of the drug persisting through 12 hours after the drug was given. Sulfonamide blood concentrations were 4 and 11 times that of the method sensitivities in the older (growing) and younger (suckling) pigs, respectively, at 48 hours after treatment. In four of the five pharmacokinetic variables studied, a significantly higher (P less than 0.01) degree of efficiency was observed in the ability of the older pigs to eliminate the drug than in the younger pigs.     

Bovine kidney tissue/biological fluid correlation for penicillin

Penicillin is one of the most commonly misused drugs in steers and dairy cows. In the US, at slaughter the tolerance is 50 ng/g in kidney and other edible tissues. If the tolerance is exceeded, the carcass may not be used for human food. A preslaughter test for penicillin in an easily accessible biological fluid is needed to predict if the concentration of penicillin is below tolerance in the kidney before the bovine is slaughtered. In this study, 12 steers were injected three times with the approved dose (7000 IU) of penicillin at 12-h intervals. Blood and urine samples were collected at intervals after the final dose of penicillin. At each sampling point, one kidney biopsy sample was collected by laparoscopic surgery in the live animal. Another kidney sample was collected at slaughter. Correlations between plasma and kidney concentrations and between urine and kidney concentrations were determined. These correlations predict with 95% confidence that 99% of the animals will have kidney tissue below penicillin tolerance when the plasma concentration of penicillin is below 0.4 ng/mL and/or the urine penicillin concentration is below 140 ng/mL.     

Copper, zinc and manganese concentrations in equine liver, kidney and plasma

Five groups of horses were fed different diets of known trace mineral concentration for a minimum of six months. Copper (Cu), zinc (Zn) and manganese (Mn) concentrations were measured in livers of 125 yearling horses and kidneys of 81 yearling horses as an assessment of trace mineral status. Plasma Cu and Zn determinations were made for all horses.

Mean hepatic Cu concentrations of horses fed diets containing 6.9 to 15.2 mg Cu/kg dry matter (DM) feed were 0.27 to 0.33 μmol/g DM tissue. Plasma Cu concentrations ranged between 22.8 to 28.3 μmol/L. There was no simple mathematical relationship between plasma and hepatic Cu concentrations. Mean hepatic Zn concentrations in horses fed diets containing 25.6 to 52.2 mg Zn/kg DM feed were determined to be between 2.75 to 2.91 μmol/g DM tissue. Mean plasma Zn concentrations in groups of horses were between 11.7 to 13.5 μmol/L. Plasma Zn concentrations were not indicative of hepatic Zn concentration. Hepatic Mn concentrations ranged between 0.13 and 0.14 μmol/g DM tissue.

Renal Zn concentrations ranged between 1.55 to 1.63 μmol/g DM tissue and did not differ with diet. Mean renal Mn concentrations were 0.09 μmol/g DM tissue for all groups of horses. Renal Cu concentrations ranged from 0.36 to 0.47 μmol/g DM tissue and differed with diet.

     

The enzymatic profile of urine and plasma in bovine urinary bladder cancer (enzootic bovine haematuria)

The enzymatic profile of urine and plasma in field cases of bovine bladder cancer was studied. Urinary lactate dehydrogenase activity was significantly altered along with the isoenzyme pattern. Activity of alkaline phosphatase and -glucuronidase was decreased in the affected animals. No significant changes were observed in acid phosphatase, or arylsulphatase A and B activity. In plasma, lactate dehydrogenase activity was elevated without any change in the isoenzyme pattern. No significant changes were observed in the other plasma enzymes studied or in the sialic acid concentration.     

Distribution of 5'-nucleotidase in the tissues of sheep and the effect of kidney and liver lesions on the activity of the enzyme in plasma and urine

The distribution of 5'-nucleotidase (5'-NT) activity in the tissues of the sheep differs from that of gamma glutamyl transferase (GGT). Nevertheless, both enzymes are released into the plasma of sheep which have been infected with Fasciola hepatica or in which the bile duct has been ligated. In a sheep dosed with sporidesmin, a fungal toxin which damages the biliary tract, there was an increase in GGT activity in the plasma and urine but no change in 5'-NT activity. Neither enzyme was released into the plasma or urine of sheep dosed with carbon tetrachloride. In sheep with renal tubular necrosis and hepatocellular necrosis caused by dosage with hexachlorobutadiene, both enzymes were released into the plasma, and GGT, but not 5'-NT activity was found in urine. In sheep with tubular necrosis of the kidney caused by the administration of mercuric chloride, GGT activity, but not 5'-NT, increased in the plasma and urine.     

The distribution of vitamin A and retinol-binding protein in the blood plasma, urine, liver and kidneys of carnivores

The contents of retinol and retinyl esters as well as retinol-binding protein (RBP) in the plasma, urine, liver and kidneys of dogs, raccoon dogs and silver foxes were investigated. In the plasma and urine of all three species, vitamin A was present as retinol and retinyl esters. Vitamin A levels (1376+/-669 microg x g(-1)) were significantly higher in the livers of dogs than in the kidneys (200+/-217 microg x g(-1), P < 0.001 ). However, vitamin A levels in the kidneys of raccoon dogs (291+/-146 microg x g(-1)) and silver foxes (474+/-200 microg x g(-1)) were significantly higher than in the liver (67+/-58 microg x g(-1) and 4.3+/-2.4 microg x g(-1), respectively, both P < 0.001). RBP was immunologically detected in the blood plasma of all species, but never in the urine. In the liver, immunoreactive RBP was found in hepatocytes. In the kidneys of all species, RBP was observed in the cells of the proximal convoluted tubules. The levels of vitamin A in the livers of raccoon dogs and silver foxes were extremely low, which would be interpreted as a sign of great deficiency in humans. This observation might indicate that the liver status cannot be used as an indicator of vitamin A deficiency in canines. The high levels of vitamin A in the kidneys in all three species may indicate a specific function of the kidney in the vitamin A metabolism of canines.     

Tissue disposition and depletion of penicillin G after oral administration with milk in unweaned dairy calves

OBJECTIVE: To determine tissue depletion of penicillin G in calves after oral ingestion with milk replacer and estimate a withdrawal period. DESIGN: Longitudinal controlled trial. ANIMALS: 26 Holstein calves. PROCEDURE: Once daily, 24 calves were fed milk replacer containing procaine penicillin G (0.68 mg/kg [0.31 mg/lb] of body weight); 2 calves served as controls. After 1 feeding, 12 calves were euthanatized in groups of 3 each 4, 6.5, 9.5, and 13 hours after feeding. After 14 days, 12 calves were euthanatized in groups of 3 each 4, 6.5, 9.5, and 13 hours after the final feeding. Concentrations of penicillin G were determined in tissues, blood, and urine by use of high-performance liquid chromatography. RESULTS: Penicillin G was not detected in muscle samples of treated calves. The highest concentrations of penicillin G in plasma, kidney, and liver were 13 ng/ml, 92 ng/g, and 142 ng/g, respectively. Thirteen carcasses had violative drug residues; 12 had violative residues in the liver only, and 1 had violative residues in the liver and kidney. A 21-hour withdrawal period was estimated. CONCLUSIONS AND CLINICAL RELEVANCE: Liver had the highest concentration of penicillin G and was most likely to have violative residues. Feeding calves milk containing penicillin G has the potential to cause violative drug residues in tissues. It is recommended to observe an appropriate withdrawal time prior to slaughter if calves are fed milk from cows treated with penicillin G.     

Pharmacokinetics of tildipirosin in bovine plasma,lung tissue,and bronchial fluid (from live,nonanesthetized cattle)

Menge, M., Rose, M., Bohland, C., Zschiesche, E., Kilp, S., Metz, W., Allan, M., Röpke, R., Nürnberger, M. Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle). J. vet. Pharmacol. Therap.  35 , 550–559. The pharmacokinetics of tildipirosin (Zuprevo^® 180 mg/mL solution for injection for cattle), a novel 16‐membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (C_max) was 0.7 μg/mL. T_max was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRT_last) and terminal half‐life (T_1/2) was 6 and 9 days, respectively. A strong dose–response relationship with no significant sex effect was shown for both C_max and area under the plasma concentration–time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUC_last) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (V_z) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time–concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T_1/2 in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination.     

A gas-chromatographic headspace method for the determination of acetone in bovine milk, blood and urine

An automated headspace gas-chromatographic method has been developed for the determination of acetone in the milk, blood and urine of dairy cows. Five ml samples were saturated with 2 g of sodium chloride and equilibrated for 30 min at 90 degrees C in a Hewlett-Packard HP 19395 A automatic headspace sampler. The headspace volatiles were transferred without splitting to a 25 m x 0.3 mm x 0.4 microns Carbowax column in a Shimadzu GC 9A gas chromatograph, operating isothermally at 50 degrees C. The coefficients of variation for the determination of acetone were 1.5-4.4% for urine, 10.0-24.9% for milk and 2.0-19.6% for blood. The detection limits were 0.0055 mg/100 ml for milk, 0.0072 mg/100 ml for blood and 0.0080 mg/100 ml for urine. The analysis time of 5 min per sample provided an adequate rate of throughput for routine monitoring.     

The correlation of potassium content and moisture in bovine liver samples analyzed for trace mineral concentrations.

Beef cattle in the United States are often found to be deficient in essential trace minerals such as copper and zinc. Established reference ranges for mineral concentrations exist and usually designate a concentration as adequate, marginal, deficient, or excessive. This research investigates a new method of interpreting detected elemental concentrations in bovine liver that will add confidence to the final diagnosis. This is based on the hypothesis that a correlation exists between potassium concentration and moisture in a bovine liver sample. This relationship between potassium and moisture content enables the diagnostician to more accurately predict mineral concentrations and wet weight regardless of sample moisture loss. Correlations were found between potassium content and percentage of moisture in experimental samples, clinical biopsies, and a validation study, to a statistical significance of P < 0.001. Experimental samples had a correlation coefficient of R2 = 0.95 and the mathematical relationship y = 2513.2x(-1.0662). Clinical biopsies had a correlation of R2 = 0.83 and the mathematical relationship y = 2203.4x(-0.991). The validation study had a correlation of R2 = 0.55 and a mathematical relationship y = 2321.4x(-0.952). An exponent of -1 is predicted by conservation of potassium mass. These findings have practical significance in maintaining and improving cattle growth, health, reproduction, and food safety.     

Content of retinol and retinyl esters in blood plasma,liver, kidney and reproductive organs of Japanese quails

Due to its importance in many physiological processes such as cell proliferation and differentiation, vitamin A plays a key role in reproduction. The present study examines the content and distribution of retinol and retinyl esters in the blood plasma, liver, kidney, ovary and oviduct (infundibulum, magnum, isthmus and uterus) of the laying Japanese quail. (1) The results show that the stage of egg laying had no influence on the level of vitamin A (retinol or retinyl esters) in plasma, kidney and liver. (2) The results further indicate that in the oviduct there are quantitative and qualitative differences in the concentration of retinol and retinyl esters, but that these differences are not altered by the stage of egg formation. (3) The highest levels of vitamin A in the isthmus and uterus were associated with a predominance of retinyl esters (palmitate and stearate); sections with lower total levels of vitamin A (infundibulum, magnum) had retinol as the more dominant form of vitamin A. (4) Changes in the ratio of retinol to retinyl esters in the various sections of the avian oviduct might point to metabolic differences. The storage of vitamin A might therefore be the predominant function of the uterus and isthmus; in the infundibulum and magnum, where vitamin A is predominantly present as retinol, vitamin A serves rather as a precursor for the modulation of the cellular metabolism of these structures.     

Correlation between oral fluid and plasma oxytetracycline concentrations after intramuscular administration in pigs

The penetration of oxytetracycline (OTC) into the oral fluid and plasma of pigs and correlation between oral fluid and plasma were evaluated after a single intramuscular (i.m.) dose of 20 mg/kg body weight of long‐acting formulation. The OTC was detectable both in oral fluid and plasma from 1 hr up to 21 day after drug administration. The maximum concentrations (C_max) of drug with values of 4021 ± 836 ng/ml in oral fluid and 4447 ± 735 ng/ml in plasma were reached (T_max) at 2 and 1 hr after drug administration respectively. The area under concentration–time curve (AUC), mean residence time (MRT) and the elimination half‐life (t_1/2β) were, respectively, 75613 ng × hr/ml, 62.8 hr and 117 hr in oral fluid and 115314 ng × hr/ml, 31.4 hr and 59.2 hr in plasma. The OTC concentrations were remained higher in plasma for 48 hr. After this time, OTC reached greater level in oral fluid. The strong correlation (r = .92) between oral fluid and plasma OTC concentrations was observed. Concentrations of OTC were within the therapeutic levels for most sensitive micro‐organism in pigs (above MIC values) for 48 hr after drug administration, both in the plasma and in oral fluid.     

Multielement assays of canine serum, liver, and kidney by inductively coupled argon plasma emission spectroscopy

Inductively coupled argon plasma emission spectroscopy was used to measure Al, As, Ca, Cd, Cr, Cu, Fe, Pb, Mg, Mn, Hg, Mo, P, K, Se, Na, Tl, and Zn in canine specimens (70 serum, 270 liver, and 200 kidney). Mean concentrations of each of these elements in detectable amounts in these samples were established, and histograms of the concentration distributions of elements in the samples were developed.     

Disposition of methylprednisolone acetate in plasma,urine, and synovial fluid following intra‐articular administration to exercised thoroughbred horses

Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time‐related urine and synovial fluid concentrations following intra‐articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra‐articular administration of MPA (100 mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77 days postdrug administration and analyzed using tandem liquid chromatography‐mass spectrometry (LC‐MS/MS). Maximum measured plasma MPA concentrations were 6.06 ± 1.57 at 0.271 days (6.5 h; range: 5.0–7.92 h) and 6.27 ± 1.29 ng/mL at 0.276 days (6.6 h; range: 4.03–12.0 h) for horses that had synovial fluid collected (group 1) and those that did not (group 2), respectively. The plasma terminal half‐life was 1.33 ± 0.80 and 0.843 ± 0.414 days for groups 1 and 2, respectively. MPA was undetectable by day 6.25 ± 2.12 (group 1) and 4.81 ± 2.56 (group 2) in plasma and day 17 (group 1) and 14 (group 2) in urine. MPA concentrations in synovial fluid remained above the limit of detection (LOD) for up to 77 days following intra‐articular administration, suggesting that plasma and urine concentrations are not a good indicator of synovial fluid concentrations.     

Disposition of sulfadimethoxine in camels (Camelus dromedarius) following single intravenous and oral doses.

Single-dose pharmacokinetics of sulfadimethoxine were determined in six adult camels (Camelus dromedarius) following administration of a mean dosage of 17.5 +/- 2.7 mg/kg both i.v. and p.o. Serial blood samples were collected through an indwelling jugular catheter intermittently for 5 days for both routes. Sulfadimethoxine was assayed using high-performance liquid chromatography. Serum drug concentration versus time data for each animal was subjected to linear regression, with the best-fit model selected based on residual analysis. The data fit best into a two-compartment open model, with first-order input for oral administration. For orally administered drug, mean maximum serum concentration of 19.3 +/- 1.7 microg/ml was reached at 11.41 +/- 2.59 hr, with an elimination rate constant of 0.09/hr +/- 0.05/hr and an elimination half-life of 11.7 +/- 3 hr. Mean peak serum concentration following i.v. administration was 223 +/- 48 microg/ml. Mean volume of distribution at steady state was 0.393 +/- 0.049 L/kg. Elimination rate constants differed with i.v. and oral administration, suggesting a flip-flop model. Oral bioavailability was 103% +/- 38%. Comparison of maximum serum concentrations to the microbial breakpoint concentration reported for sulfadimethoxine (512 microg/ml) suggests that the dose used in this study, 17.5 +/- 2.7 mg/kg, is insufficient for achieving therapeutic serum levels.