Practical oxygen therapy for newborn piglets.

Aims: To evaluate the effect of a novel method of practical oxygen therapy on physiological parameters related to survival, weaning weight and preweaning mortality of neonatal piglets under commercial farm conditions. Methods: Piglets from hyperprolific sows born with signs of asphyxia, (n = 109; <6 on a score of respiration, meconium staining and activity) or very low birth weight (VLBW; n = 112; <1.05 kg) were selected for the study. Approximately half of each group (n = 55 VLBW piglets and n = 57 piglets with asphyxia) received 100% oxygen immediately after birth using a specially designed facemask for 45 seconds (VLBW) or 1 minute (asphyxiated). Physiological parameters (peripheral blood oxygen saturation (SpO2) blood glucose concentration and rectal temperature) were measured before oxygen treatment 5 minutes after birth (SpO2) and 24 hours later (SpO2, blood glucose concentration, temperature). Weight at birth, at 24 hours and at 21 days of age, preweaning mortality, and estimated colostrum intake were also recorded. Results: A significant treatment effect on SpO2 was observed (p = 0.013 and p < 0.001 for VLBW and asphyxiated piglets respectively). VLBW and asphyxiated piglets that received oxygen treatment had higher SpO2 after treatment (measured 5 minutes after birth, 97.7 and 97.8% respectively) compared to immediately after birth (93.3 and 86.8% respectively) while untreated piglets showed no variation. Blood glucose concentrations increased in all piglets between birth and 24 hours of age (p = 0.003 and p < 0.001 for asphyxiated and VLBW piglets respectively) and this was higher in asphyxiated piglets that received oxygen than those that did not (5.6 (SE 0.2) mmol/L; p < 0.05). Estimated colostrum intake was higher in asphyxiated (401.6 (SD 24.4) g/kg) and VLBW (374.9 (SE 23.4 g/kg) piglets that received oxygen than those that did not (273.2 (SE 24.1) g/kg; p < 0.001 and 249.0 (SE 22.5) g/kg; p < 0.001 respectively). Similarly weight at weaning was higher in asphyxiated (5.8 (SE 0.2) kg) and VLBW (4.9 (SE 0.2) kg) piglets that received oxygen therapy than control animals (4.9 (SE 0.2) kg; = 0.005 and 4.1 (SE 0.2) kg; p = 0.008 respectively). Furthermore, oxygen treatment markedly reduced preweaning mortality from 9/52 (17%) untreated to 1/57 (1.7%) oxygen-treated piglets suffering asphyxia at birth (p = 0.006). Conclusions: Oxygen therapy improves physiological and productive parameters in piglets born with signs of asphyxia or VLBW. The incorporation of this strategy as part of the farrowing routine enhances the advantages of rearing hyperprolific sows.

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.

Fosfomycin: Uses and potentialities in veterinary medicine.

Fosfomycin (FOS) is a natural bactericidal broad-spectrum antibiotic which acts on proliferating bacteria by inhibiting cell wall and early murein/peptidoglycan synthesis. Bactericidal activity is evident against Gram positive and Gram negative bacteria and can also act synergistically with other antibiotics. Bacterial resistance to FOS may be natural or acquired. Other properties of this drug include inhibition of bacterial adhesion to epithelial cells, exopolysaccharide biofilm penetration, immunomodulatory effect, phagocytosis promotion and protection against the nephrotoxicity caused by other drugs. FOS has chemical characteristics not typically observed in organic phosphoric compounds and its molecular weight is almost the lowest of all the antimicrobials. It tends to form salts easily due to its acidic nature (disodium salt, for intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration; calcium and trometamol salt: for oral (PO) administration). FOS has a very low protein binding (<0.5%) which, along with its low molecular weight and water solubility, contributes to its good diffusion into fluids (cerebrospinal fluid, aqueous and vitreous humor, interstitial fluid) and tissues (placenta, bone, muscle, liver, kidney and skin/fat). In all species, important differences in the bioavailability have been found after administration in relation to the various derivatives of FOS salts. Pharmacokinetic profiles have been described in humans, chickens, rabbits, cows, dogs, horses and weaning piglets. The low toxicity and potential efficacy of FOS are the main factors that contribute to its use in humans and animals. Thus, it has been used to treat a broad variety of bacterial infections in humans, such as localized peritonitis, brain abscesses, severe soft tissue infections, cystitis and other conditions. In veterinary medicine, FOS is used to treat infectious diseases of broiler chickens and pigs. In broilers, it is administered for the treatment of E. coli and Salmonella spp. infections. In piglets, the drug is prescribed to treat a wide variety of bacterial infections. FOS penetration is demonstrated in phagocytic, respiratory (HEP-2) and intestinal (IPEC-J2) cells. Although not widely used in animals, the drug has shown good results in human medicine. The potentialities of FOS suggest that this drug is a promising candidate for the treatment of infections in veterinary medicine. For these reasons, the aim of this work is to provide animal health practitioners with information on a drug that is not extensively recognized.

Efficacy of free glutathione and niosomal glutathione in the treatment of acetaminophen-induced hepatotoxicity in cats.

Acetaminophen (APAP) administration results in hepatotoxicity and hematotoxicity in cats. The response to three different treatments against APAP poisoning was evaluated. Free glutathione (GSH) (200mg/kg), niosomal GSH (14 mg/kg) and free amino acids (180 mg/kg of N-acetylcysteine and 280 mg/kg of methionine) were administered to cats that were intoxicated with APAP (a single dose of 150 mg/kg, p.o.). Serum concentration of alanine aminotransferase (ALT) along with serum, liver and erythrocyte concentration of GSH and methemoglobin percentage were measured before and 4, 24 and 72 hours after APAP administration. Free GSH (200 mg/kg) and niosomal GSH (14 mg/kg) were effective in reducing hepatotoxicity and hematotoxicity in cats intoxicated with a dose of 150 mg/kg APAP. We conclude that both types of treatments can protect the liver and haemoglobin against oxidative stress in APAP intoxicated cats. Furthermore, our results showed that treatment with niosomal GSH represents an effective therapeutic approach for APAP poisoning.

Disodium-fosfomycin pharmacokinetics and bioavailability in post weaning piglets.

Disodium-fosfomycin pharmacokinetics has been studied in different species after oral, intravenous, intramuscular and subcutaneous administration. At present there are neither documented clinical experiences of the use of fosfomycin in pigs nor any published studies in weaning piglets, although it is a period of high incidence of infectious diseases. The pharmacokinetics and the bioavailability of sodium fosfomycin were studied in post weaning piglets after intravenous and intramuscular administration of 15 mg/kg of body weight. Plasma concentrations were measured by a high-performance liquid ms/ms. After IV administration the area under the fosfomycin concentration:time curve in plasma was AUC(0-12) of 120.00 ± 23.12 µg h/ml and the volume of distribution (Vd) of 273.00 ± 40.70 ml/kg. The elimination was rapid with a plasma clearance of 131.50 ± 30.07 ml/kg/h and a T(1/2) of 1.54 ± 0.40 h. Peak serum concentration (Cmax), Tmax, AUC(0-12) and bioavailability for the IM administration were 43.00 ± 4.10 µg/ml, 0.75 ± 0.00 h, 99.00 ± 0.70 µg h/ml and 85.5 ± 9.90% respectively. Different authors have determined a minimum inhibitory concentration (MIC90) ranging from 0.25 µg/ml for Streptococcus sp. and 0.5 µg/ml for Escherichia coli. Considering the above, and according to the values of plasma concentration vs time profiles observed in this study, effective plasma concentrations of fosfomycin for sensitive bacteria can be obtained following IV and IM administration of 15 mg/kg in piglets.

The disposition of free and niosomally encapsulated Rac-flurbiprofen in dairy bovines.

Pharmacokinetic parameters were established for flurbiprofen (FBP) after intravenous (i.v.) administration (0.5 mg/kg) of niosomal and nonniosomal formulations in dairy cattle. Niosomes of FBP showed a drug loading of 92.0 +/- 0.7% and the intravenous administration of the FBP niosomes to dairy cattle did not produce any immunological reaction associated to niosomal components. Niosomal FBP was slowly eliminated from plasma and mean residual time (MRT) and AUC(0-->t) and t (1/2) values were significantly higher than those for non niosomal FBP formulations. The results presented in this study indicate that the long circulation of FBP niosomes offers a potential application for improving the pharmacokinetic parameters of short half-life drugs for clinical use. Niosomes offer new promising perspectives of drug delivery modules in bovine therapeutics.

Pharmacokinetics and synovial fluid concentrations of flurbiprofen enantiomers in horses: chiral inversion.

Flurbirpofen (FBP), a member of the 2-aryl propionate nonsteroidal anti-inflammatory drug class, has potent anti-inflammatory and analgesic properties. The commercial preparation is a racemic mixture of the R(-) and S(+) enantiomers of FBP. In this study, R(-) and S(+) FBP were used to investigate the metabolic chiral inversion. Each enantiomer was administered separately (0.25 mg/kg) and in a racemic mixture (0.5 mg/kg) intravenously to horses. Plasma and synovial concentration of each enantiomer was determined and the disposition of each was analyzed. After intravenous administration of R(-) FBP and S(+) FBP to horses no chiral inversion was detected. After the administration of the FBP racemate and individual enantiomers no differences were observed between pharmacokinetic parameters [t(1/2beta) (h), Cl (L/h.kg), AUC (microg.h/mL), Vss (L/kg) and MRT (h)] for R(-) and S(+) FBF. Synovial fluid concentrations of both FBP enantiomers were lower than plasma concentrations and no stereoselective differences were detected. These data indicate that the disposition of FBF in horses is not enantioselective and demonstrate a difference in the pharmacokinetic behavior of the enantiomers as compared with other 2-aryl-propionic acids, such as carprofen, ketoprofen and vedaprofen in the horse.

Disposition of suprofen enantiomers in the cat.

Suprofen (SPF) is a non-steroidal anti-inflammatory drug (NSAID), which belongs to the 2-arylpropionic acids subclass. As a result of their chiral characteristics, these compounds have shown a marked enantioselective behaviour with a high degree of interspecies variation. They are mainly eliminated by glucuronidation. Plasma, biliary and urine disposition of SPF was investigated in the cat after intravenous administration of the racemate (dose 2 mg/kg). Both enantiomers exhibited similar disposition profiles in plasma with no evidence of chiral inversion. During bile sampling time, recovered acylglucuronides of R (-) and S (+) SPF were less than 1% of the total dose administered. Only free SPF was recovered in the urine, representing 0.12% of the administered racemic SPF dose. The results indicate that neither chiral inversion nor glucuronidation predominate in SPF disposition in cats.

Enantioselective behaviour of drugs used in domestic animals: a review.

The chirality of drugs, with particular reference to agents used in veterinary medicine, is reviewed. Basic concepts of chirality and aspects of the methodology for the separation of enantiomers are considered. Chiral compounds are in common use in animals and their pharmacological actions and side-effects (pharmacodynamics) and absorption into and fate within the body (pharmacokinetics) are of fundamental importance; pharmacodynamic and pharmacokinetic properties of enantiomeric pairs commonly differ and this has major implications for their effective and safe therapeutic use. As examples of the particular significance of chirality in veterinary medicine, the following drug classes are reviewed; benzimidazole anthelmintics, cloprostenol, verapamil, ketamine, halogenated hydrocarbon anaesthetics and 2-arylpropionic acid anti-inflammatory drugs. The implications of chirality for drug product development and approval by registration authorities are discussed.

Pharmacokinetics of cefoperazone in horses.

The pharmacokinetics and bioavailability of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase (t1/2 (alpha): 4.22 +/- 2.73 min) was followed by a slower elimination phase (t1/2(beta) 0.77 +/- 0.19 h). The apparent volume of distribution was 0.68 +/- 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 +/- 0.74 microgram/mliter. After IM administration a bioavailability of 42.00 +/- 5.33% was obtained. Half-life of absorption was 2.51 +/- 0.72 min and t1/2(beta) was 1.52 +/- 0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91 +/- 0.85 microgram/mliter and 5.56 +/- 0.70 microgram/mliter, respectively.

Pharmacokinetics of ticarcillin and ticarcillin-probenecid in sheep.

Serum concentrations of ticarcillin were measured serially over a period of 12h in a cross over trial involving 6 healthy adult ewes after intravenous and intramuscular (IM) administration of 40 mg ticarcillin per kg body weight. Probenecid (40 mg/kg) was also administered IM immediately before the IM administration of 40 mg/kg ticarcillin. Pharmacokinetic values after intravenous administration were: half-life of elimination (T 1/2 beta) = 0.90 +/- 0.09 h; volume of distribution at steady state (Vdss) = 456.8 +/- 106.6 ml/kg, total body clearance (CIB) = 614.5 +/- 81.2 ml/h/kg. Ticarcillin persisted in serum at greater than or equal to 1.5 micrograms/ml for 4 hours. Pharmacokinetic and bioavailability values after intramuscular administration were: half-life of absorption (T 1/2 ab) = 8.08 +/- 1.98 min; T 1/2 beta = 0.96 +/- 0.07 h. Peak serum concentration (Cmax) was 31.11 +/- 6.02 micrograms/ml at 0.50 h (Tmax), bioavailability (F) was 0.82 +/- 0.09. After ticarcillin was administered IM together with probenecid the T 1/2 ab was 33.9 +/- 13.7 min, the T 1/2 beta 2.66 +/- 0.65 h, Cmax = 44.87 +/- 5.58 at 1.33 +/- 0.44 h, and F = 1.25 +/- 0.23.