A Field Study of Serum,Colostrum, Milk Iodine,and Thyroid Hormone Concentrations in Postpartum Draft Mares and Foals

Iodine, thyroxine (T4) and triiodothyronine (T3) are required for normal fetal growth, maturation, and neonatal survival. There is a lack of robust information on iodine levels found in colostrum, milk, and serum of mares and foals after a healthy pregnancy. Our objective was to characterize colostrum, milk, and serum iodine levels in healthy postpartum mares and foals (n = 10) and explore relationships with thyroid hormone concentrations. Colostrum, milk, and jugular blood samples from draft breed mares and foals with an estimated average iodine daily intake of 39 mg per mare during pregnancy were obtained at Day 0 (foaling date) and/or 10 days later. Parameters studied were (1) mare basal concentrations of serum: TT3, TT4, and iodine; (2) iodine in colostrum at Day 0 and milk iodine (Day 10); and (3) foal basal: TT3, TT4, and serum iodine (Days 0 and 10). Median ± median error colostrum iodine levels (165 ± 15.1 μg/L) were higher than milk (48 ± 5.6 μg/L; P = .007) levels. Median ± median error foal serum iodine (268.5 ± 7.6 μg/L), TT4 (1,225 ± 47.8 nmol/L), and TT3 (14.2 ± 1.1 nmol/L) at foaling date were higher than at 10 days (serum iodine: 70 ± 3.6 μg/L; TT4: 69.6. ± 20.4 nmol/L; and TT3: 5.4 ± 0.3 nmol/L). In conclusion, equine mammary tissue concentrates iodine beyond plasma levels, making colostrum and milk a significant source of iodine. Foal serum iodine levels are high in the neonatal period and are positively correlated with TT4, which is important for neonatal adaptation.     

Disposition of ampicillin trihydrate in plasma,uterine tissue,lochial fluid,and milk of postpartum dairy cattle

The objective of this study was to determine the disposition of ampicillin in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle. Ampicillin trihydrate was administered by intramuscular (i.m.) injection at a dose of 11 mg/kg of body weight every 24 h (n = 6, total of 3 doses) or every 12 h (n = 6, total of 5 doses) for 3 days. Concentrations of ampicillin were measured in plasma, uterine tissue, lochial fluid, and milk using HPLC with ultraviolet absorption. Quantifiable ampicillin concentrations were found in plasma, milk, and lochial fluid of all cattle within 30 min, 4 h, and 4 h of administration of ampicillin trihydrate, respectively. There was no significant effect of dosing interval (every 12 vs. every 24 h) and no significant interactions between dosing interval and sampling site on the pharmacokinetic variable measured or calculated. Median peak ampicillin concentration at steady‐state was significantly higher in lochial fluid (5.27 μg/mL after q 24 h dosing) than other body fluids or tissues and significantly higher in plasma (3.11 μg/mL) compared to milk (0.49 μg/mL) or endometrial tissue (1.55 μg/mL). Ampicillin trihydrate administered once daily by the i.m. route at the label dose of 11 mg/kg of body weight achieves therapeutic concentrations in the milk, lochial fluid, and endometrial tissue of healthy postpartum dairy cattle.     

Effect of quality of colostrum on health,growth and immunoglobulin G concentration in Holstein calves in a hot environment

The aim of this study was to determine the effect of ingestion of pasteurized and subsequently frozen–thawed pooled colostrum (≥50 mg Ig/mL) with different bacterial counts and immunoglobulin concentration (IgC) on the occurrence of diarrhea and pneumonia in 306 neonatal Holstein calves in a hot environment. Calves were assigned to be fed colostrum with total bacterial counts (TBC) lower or greater than 100 000 colony‐forming units (cfu)/mL, total coliform counts (TCC) greater or lower than 10 000 cfu/mL, and IgC lower or higher than 85 mg Ig/mL. Calves fed colostrum with TBC ≥100 000 cfu/mL were more likely (risk ratio 1.34, confidence interval 1.05–1.71; P < 0.05) to present pneumonia than calves receiving colostrum with lower TBC (incidence 53.2 vs. 39.8%). Calves fed colostrum with high TCC had increased chances of suffering pneumonia (51.4 vs. 42.1%; P < 0.05) than calves fed colostrum with lower TCC. Calves fed colostrum with ≥85 mg Ig/mL tended to present higher daily weight gain (505 ± 113 vs. 484 ± 126 g; P = 0.09). TBC and TCC in colostrum did not influence the incidence rate of diarrhea. It was concluded that under the conditions of the present study, heavy contamination of on‐farm pasteurized frozen–thawed colostrum is seemingly unavoidable and this contamination poses a threat for pneumonia, but not for diarrhea.     

Pharmacokinetics of tobramycin following intravenous,intramuscular, and intra‐articular administration in healthy horses

The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra‐articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3‐way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half‐life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (C_max) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0–2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on C_max:MIC of 10.     

Protein digestibility of porcine colostrum by neonatal pigs

Colostrum plays an important role in neonatal growth and development. However, little is known about the digestion of macronutrients in colostrum of any species. This study was conducted with the neonatal piglet model to determine the digestibility of proteins in porcine colostrum. Twelve, 1-d-old, male piglets were selected from 3 litters (4 pigs/litter) and housed individually in metabolism crates with heating lamps to maintain a temperature of 35 °C. Colostrum (13 L) was collected from 400 sows (30 to 40 mL/sow) within 12 h postpartum after injection of oxytocin. All piglets were fed colostrum containing 0.25% (DM basis) chromium oxide as an external marker based on the following feeding program: 6 meals/d for an entire 3-d period; with 40 mL/meal for d 1 (240 mL/d), 55 mL/meal for d 2 (330 mL/d), and 70 mL/meal for d 3 (420 mL/d). Colostrum was hand-fed using baby milk bottles. Entire fecal samples with the chromium green color were collected each day after colostrum feeding. Fecal collection was terminated before the fading of the green color. Fecal samples were weighed (10.3 ± 1.0 g/pig), stored in − 20 °C, freeze-dried, and thoroughly ground for chemical analysis. Blood samples were collected at 0900 h of d 3 to obtain plasma samples for amino acid and immunoglobulin (Ig) G analysis. Digestibilities of crude protein and DM in colostrum, defined as the percentage of ingested colostral crude proteins and DM that disappeared in the gut, averaged 96.9 ± 0.4% and 98.3 ± 0.2%, respectively. Digestibility of total amino acids (protein-bound plus free amino acids) in the colostrum was 98.3 ± 0.1%, with the values being 98.5 ± 0.3, 98.2 ± 0.4, and 98.3 ± 0.3%, respectively, for Lys, Thr, and Arg. Plasma and colostral IgG content were 3.4 ± 0.3 and 3.8 ± 0.7 g/L, respectively. In conclusion, protein-bound and free amino acids in porcine colostrum were highly digestible and available to neonatal pigs.     

Blood and Colostrum/Milk Serum γ‐Glutamyltransferase Activity as a Predictor of Passive Transfer Status in Lambs

The importance of blood and colostrum/milk serum γ‐glutamyl transferase (γ‐GT) enzyme activity was evaluated to assess passive transfer status in healthy lambs. Thirty Akkaraman sheep (3–6 years old) were used which had normal pregnancy period and the same conditions, and the age of the lambs ranged between 0 and 15 days. Blood and colostrum/milk samples were collected from sheep and lambs after birth, before suckling (0) and after on 1st, 3rd, 7th and 15th days. Serum immunoglobulin G (IgG) concentration was determined by the use of Single Radial Immunodiffusion method. Serum γ‐GT activity was measured, using a commercially available kit in blood and colostrum/milk samples. Correlations were carried out between immunoglobulin and γ‐GT levels. Regression models (simple and multiple) were calculated with significant data. Linear correlation was determined between colostrum/milk γ‐GT activity and IgG concentrations and between serum γ‐GT activity and IgG concentrations in lambs on the 0 day. (r: 0.607, P: 0.001), 1st (r: 0.768, P: 0.001) and the 3rd (r: 0.603, P: 0.001) days and on the 1st (r: 0.637, P: 0.001) and 3rd (r: 0.478, P: 0.012) days in the experiment, respectively. Multivariate regression models were developed to estimate sample IgG concentration. Serum and colostrum/milk IgG concentration could be predicted using the formula: lamb serum IgG = 825 + 0.688 (lamb γ‐GT) + 52 (days); colostrum/milk IgG = 832 + 0.505 (colostrum/milk γ‐GT) ? 167 (days). The regression models were moderately accurate in predicting serum IgG concentration (R² = 0.51) and colostrum/milk IgG concentration (R² = 0.55). Test sensitivity and positive predictive values for serum γ‐GT enzyme activity were found to be 96 and 100% and for colostrum/milk γ‐GT enzyme activity were found to be 100 and 68% to prediction IgG concentration. Serum and colostrum/milk γ‐GT activity can be used to assess passive transfer status of lambs. Along with this, regression models used to calculate serum and colostrum/milk γ‐GT activities found to be useful to estimate sample IgG concentration. The use of serum and colostrum/milk γ‐GT enzyme activity was found useful especially after birth on the 0, 1st and 3rd days.     

Leptin and ghrelin levels in colostrum,milk and blood plasma of sows and pig neonates during the first week of lactation

Radioimmunology was used to determine leptin and ghrelin levels in sow colostrum and milk in relation to those in sow and neonatal pig blood plasma and to the body weight of piglets during the first week of lactation. The highest concentration of leptin was found in colostrum on the second day of lactation (69.3 ± 6.3 ng/mL). Leptin concentrations in sow plasma were significantly lower than in colostrum/milk (2.19 ± 0.9 ng/mL, P = 0.7692) and were stable in the first 7 days of lactation. Total and active ghrelin concentrations in colostrum/milk were stable in the measured time points (6734 ± 261 pg/mL, P = 0.3397; 831 ± 242 pg/mL, P = 0.3988, respectively). Total ghrelin concentrations in sow plasma were lower than in colostrum/milk. These results indicate that pigs follow a unique species‐specific pattern of leptin and ghrelin synthesis, release and existence, and that the mammary gland is an important source of leptin and ghrelin contained in colostrum/milk.     

Development of intraosseous infusion of the distal phalanx to access the foot lamellar circulation in the standing,conscious horse

Intraosseous (IO) infusion of the distal phalanx (IOIDP) as a delivery route targeting hoof lamellar tissue of standing, conscious horses was evaluated. Following sedation and regional nerve blockade in six Standardbred horses, a microdialysis (MD) probe was implanted into the hoof lamellar tissue of one forelimb. A purpose designed cannulated bone screw was introduced into the body of the distal phalanx, approximately 6 cm from the MD probe. Gentamicin solution (25 mg/mL) was infused at 20 μL/min through the bone screw for 2 h without the application of a tourniquet. MD and blood samples were collected at regular intervals and analysed for gentamicin concentrations.Gentamicin was present in lamellar tissue at much higher concentrations than peripheral serum. The mean concentration of gentamicin was 24.4, 20.5 and 4.4 μg/mL in extracellular fluid (ECF) and 0.28, 0.5 and 0.32 μg/mL in serum samples collected 60, 120 and 150 min after IOIDP was started, respectively. A clinically safe and efficacious IO drug delivery to the hoof lamellar tissue of standing, conscious horse was developed.     

Depletion of florfenicol in lactating dairy cows after intramammary and subcutaneous administration

Eighteen Holstein dairy cows ranging in body weight from 500–700 kg and with an average milk yield of 37 ± 6 kg/day were used to investigate the depletion of florfenicol (FFL) in milk and plasma of dairy cows. Three groups of six were administered FFL: Group A, intramammary (IMM) infusion of ~2.5 mg FFL/kg BW at three consecutive milking intervals (total amount of ~7.5 mg/kg BW); Group B, one IMM infusion (20 mg/kg BW) into one quarter and Group C, one subcutaneous (SC) treatment (40 mg/kg BW). IMM infusions were into the right front quarter. Cows were milked daily at 06:00 and 18:00 h. The highest concentrations (C_max) and time to C_max (T_max) were: 1.6 ± 2.2 μg·FFL/mL milk at 22 h (Group A), 5.5 ± 3.6 μg·FFL/mL milk at 12 h (Group B), and 1.7 ± 0.4 μg·FFL/mL milk at 12 h (Group C). The half‐lives (t_1/2) were ~19, 5.5, and 60 h, for Groups A, B, and C, respectively. FFL was below the limit of detection (LOD) by 60 h in three Group B cows, but above the LOD at 72, 84, and 120 h in three cows. FFL was above the LOD in milk from Group C's cows for 432–588 h. Plasma values followed the same trends as milk. The results demonstrate that IMM‐infused FFL is bioavailable and below the LOD within 72–120 h. The concentration of FFL was detectable in both plasma and milk over the course of 2–3 weeks after SC administration. The absence of residue depletion data presents problems in determining safe levels of FFL residues in milk and edible tissues. The data presented here must not be construed as approval for extra‐label use in food animals.     

Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk

Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.     

Pharmacokinetics of danofloxacin and N‐desmethyldanofloxacin in adult horses and their concentration in synovial fluid

The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N‐desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N‐desmethyldanofloxacin were measured by UPLC‐MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half‐life of 8.00 ± 0.48 h. Maximum plasma concentration (C_max) of N‐desmethyldanofloxacin (0.151 ± 0.038 μg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 μg/mL) than after IG administration (0.99 ± 0.1 μg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 μg/mL) and i.m. (0.70 ± 0.35 μg/mL) than after IG (0.20 ± 0.12 μg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 μg/mL for i.v. and i.m. administration and 0.12 μg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.     

Influence of organic versus inorganic dietary selenium supplementation on the concentration of selenium in colostrum,milk and blood of beef cows

Background

Selenium (Se) is important for the postnatal development of the calf. In the first weeks of life, milk is the only source of Se for the calf and insufficient level of Se in the milk may lead to Se deficiency. Maternal Se supplementation is used to prevent this.We investigated the effect of dietary Se-enriched yeast (SY) or sodium selenite (SS) supplements on selected blood parameters and on Se concentrations in the blood, colostrum, and milk of Se-deficient Charolais cows.

Methods

Cows in late pregnancy received a mineral premix with Se (SS or SY, 50 mg Se per kg premix) or without Se (control – C). Supplementation was initiated 6 weeks before expected calving. Blood and colostrum samples were taken from the cows that had just calved (Colostral period). Additional samples were taken around 2 weeks (milk) and 5 weeks (milk and blood) after calving corresponding to Se supplementation for 6 and 12 weeks, respectively (Lactation period) for Se, biochemical and haematological analyses.

Results

Colostral period. Se concentrations in whole blood and colostrum on day 1 post partum and in colostrum on day 3 post partum were 93.0, 72.9, and 47.5 μg/L in the SY group; 68.0, 56.0 and 18.8 μg/L in the SS group; and 35.1, 27.3 and 10.5 μg/L in the C group, respectively. Differences among all the groups were significant (P < 0.01) at each sampling, just as the colostrum Se content decreases were from day 1 to day 3 in each group. The relatively smallest decrease in colostrum Se concentration was found in the SY group (P < 0.01).Lactation period. The mean Se concentrations in milk in weeks 6 and 12 of supplementation were 20.4 and 19.6 μg/L in the SY group, 8.3 and 11.9 μg/L in the SS group, and 6.9 and 6.6 μg/L in the C group, respectively. The values only differed significantly in the SS group (P < 0.05). The Se concentrations in the blood were similar to those of cows examined on the day of calving. The levels of glutathione peroxidase (GSH-Px) activity were 364.70, 283.82 and 187.46 μkat/L in the SY, SS, and C groups, respectively. This was the only significantly variable biochemical and haematological parameter.

Conclusion

Se-enriched yeast was much more effective than sodium selenite in increasing the concentration of Se in the blood, colostrum and milk, as well as the GSH-Px activity.     

Measurement of Carbonic Anhydrase Isozyme VI (CA-VI) in Bovine Sera,Saliva, Milk and Tissues

Concentrations of bovine carbonic anhydrase isozyme VI (CA-IV) in bovine serum, saliva, normal milk, colostrum, submandibular gland, liver, and mammary gland were determined. CA-VI was purified from bovine saliva and an antibody to CA-VI was generated. The concentrations of CA-VI in the saliva (7.8 ± 7.9 μg/ml), serum (2.1± 5.7 ng/ml), milk (7.9 ± 12.1 ng/ml), submandibular gland (284.7 μg/g protein), liver (921.0 ± 180.7 ng/g protein) and mammary gland (399.6 ± 191.2 ng/g protein) were determined by ELISA. No seasonal change in CA-VI levels was observed in normal milk. The concentration of CA-VI in colostrum (day 1 post partum) was 119 ng/ml and decreased rapidly by 1 month following birth. Mammary gland contained much smaller amounts than the submandibular gland. CA-VI mRNA was detected in the liver and mammary gland of cow by RT-PCR. The ELISA used in this study proved to be a precise and sensitive method for determining CA-VI concentrations in saliva, serum, milk and tissue specimens from cows. The ELISA may enable the study of changes in CA-VI associated with hereditary or metabolic disorders of the salivary gland, mammary gland and liver using small samples of saliva, serum or milk.     

Live yeast supplementation during late gestation and lactation affects reproductive performance,colostrum and milk composition,blood biochemical and immunological parameters of sows

This study was conducted to evaluate the effects of dietary live yeast (LY) supplementation during late gestation and lactation on reproductive performance, colostrum and milk composition, blood biochemical and immunological parameters of sows. A total of 40 multiparous sows were randomly fed either the control (CON) diet or the CON diet supplemented with LY at 1 g/kg from d 90 of gestation to weaning. Results showed that the number of stillborn piglets and low BW piglets were significantly decreased in the LY-supplemented sows compared with sows in the CON group (P < 0.05). Moreover, the concentrations of protein, lactose and solids-not-fat were increased in the colostrum of LY-supplemented sows (P < 0.05). Interestingly, the plasma activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (γ-GGT) at d 1 of lactation and alanine aminotransferase (ALT) at weaning day were decreased by feeding LY diet (P < 0.05). Meanwhile, sows fed LY diet had higher plasma concentration of immunoglobulin G compared with sows fed CON diet at d 1 of lactation (P < 0.05). In conclusion, LY supplementation in maternal diets decreased the number of stillborn piglets and low BW piglets, improved colostrum quality and health status of sows.     

Pharmacokinetics of ceftiofur sodium in equine pregnancy

Eleven pregnant pony mares (D270‐326) were administered ceftiofur sodium intramuscularly at 2.2 mg/kg (n = 6) or 4.4 mg/kg (n = 5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24 hr after administration. Eight pony mares were re‐enrolled in the study at least 3 days from expected foaling to ensure steady‐state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4 mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1 hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high‐performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97 ± 0.50 μg/ml (low dose) and 7.45 ± 1.05 μg/ml (high dose). Terminal half‐life was significantly (p = .014) shorter after administration of the low dose (2.91 ± 0.59 hr) than after administration of the high dose (4.10 ± 0.72 hr). The mean serum concentration of DCA from mares at time of foaling was 7.96 ± 1.39 μg/ml. The mean DCA concentration in colostrum was 1.39 ± 0.70 μg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1 μg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.     

Detection,quantifications, and pharmacokinetics of ponazuril in healthy swine

A study on pharmacokinetics of ponazuril in piglets was conducted after a single oral dose of 5.0 mg/kg b.w. Plasma concentrations were measured by high‐performance liquid chromatography assay with UV detector at 255‐nm wavelength. Pharmacokinetic parameters were derived by use of a standard noncompartmental pharmacokinetic analysis. Samples from six piglets showed good plasma concentrations of ponazuril, which peaked at 5.83 ± 0.94 μg/mL. Mean ± SD area under the plasma concentration–time curve was 1383.42 ± 363.26 h/μg/mL, and the elimination half‐life was 135.28 ± 19.03 h. Plasma concentration of ponazuril peaked at 42 h (range, 36–48 h) after administration and gradually decreased but remained detectable for up to 33 days. No adverse effects were observed during the study period. The results indicate that ponazuril was relatively well absorbed following a single dose, which makes ponazuril likely to be effective in swine.     

Pharmacokinetic evaluation of oral dantrolene in the dog

The pharmacokinetics of dantrolene and its active metabolite, 5‐hydroxydantrolene, after a single oral dose of either 5 or 10 mg/kg of dantrolene was determined. The effects of exposure to dantrolene and 5‐hydroxydantrolene on activated whole‐blood gene expression of the cytokines interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) were also investigated. When dantrolene was administered at a 5 mg/kg dose, peak plasma concentration (C_max) was 0.43 μg/mL, terminal half‐life (t_1/2) was 1.26 h, and area under the time–concentration curve (AUC) was 3.87 μg·h/mL. For the 10 mg/kg dose, C_max was 0.65 μg/mL, t_1/2 was 1.21 h, and AUC was 5.94 μg·h/mL. For all calculated parameters, however, there were large standard deviations and wide ranges noted between and within individual dogs: t_1/2, for example, ranged from 0.43 to 6.93 h, C_max ratios ranged from 1.05 to 3.39, and relative bioavailability (rF) values ranged from 0.02 to 1.56. While activated whole‐blood expression of IL‐2 and IFN‐γ as measured by qRT‐PCR was markedly suppressed following exposure to very high concentrations (30 and 50 μg/mL, respectively) of both dantrolene and 5‐hydroxydantrolene, biologically and therapeutically relevant suppression of cytokine expression did not occur at the much lower drug concentrations achieved with oral dantrolene dosing.     

Effect of sucralfate on oral minocycline absorption in healthy dogs

Sucralfate and minocycline may be administered concurrently to dogs. The relative bioavailability of tetracyclines may be reduced if administered with sucralfate, but studies confirming these interactions in dogs are not available. This study evaluated the pharmacokinetics of oral minocycline in dogs (M), determined the effects of concurrent administration of sucralfate and minocycline (MS) on minocycline pharmacokinetics, determined the effects of delaying sucralfate administration by 2 h (MS+2) on minocycline pharmacokinetics, and established dosing recommendations based on pharmacodynamic indices. Oral minocycline (300 mg) and sucralfate suspension (1 g) were administered to five greyhounds in a randomized crossover design. Minocycline plasma concentrations were evaluated using liquid chromatography with mass spectrometry. The maximum plasma concentration (C_MAX) and area under the curve (AUC) of minocycline were 1.15 μg/mL and 8.0 h* μg/mL, respectively. The C_MAX and AUC were significantly lower (P < 0.05) in the MS group (C_MAX = 0.33 μg/mL, AUC 3.0 h*μg/mL) compared with M or MS+2 (C_MAX = 0.97 μg/mL, AUC 10.3 h*μg/mL). Delaying sucralfate by 2 h did not decrease oral minocycline absorption, but concurrent administration significantly decreased minocycline absorption. A dose of 7.5 mg/kg p.o. q12 h achieves the pharmacodynamic index for a bacterial minimum inhibitory concentration (MIC) of 0.25 μg/mL (AUC:MIC≥33.9).     

Fosfomycin residues in colostrum: Impact on morpho‐physiology and microbiology of suckling piglets

Fosfomycin is a broad‐spectrum bactericidal antibiotic widely used in pig farms for the treatment of a wide variety of bacterial infections. In this study, the elimination of disodium fosfomycin in colostrum/milk of the sow and the impact of this antibiotic on the microbiota and intestinal morpho‐physiology of suckling piglets were analyzed. The average amount of fosfomycin eliminated in colostrum (after administration of 15 mg/kg IM) during the first 10 hr postpartum was 0.85 μg/ml, and the mean residual amount ingested by the piglets was 0.26 mg/kg. The elimination profile of fosfomycin concentrations in colostrum occurs at a time of profound changes in the morpho‐physiology of the gastrointestinal tract of the piglet. However, the studied concentrations did not produce imbalances on the microbiota or on the morpho‐physiology of the gastrointestinal tract of the piglet. Concentrations of fosfomycin were maintained in the mammary gland above the MIC for more than 8 hr for pathogenic bacteria of productive importance. This would indicate that fosfomycin may be considered safe for the specific treatment of bacterial infectious processes in sows during the peri‐ and postpartum period. This first study with disodium fosfomycin stimulates awareness in the proper use of antimicrobials at farrowing.