Contribution of different rumen microbial groups to gas,short‐chain fatty acid and ammonium production from different diets—an approach in an in vitro fermentation system

In this study, the relative contribution of different microbial groups to ruminal metabolism was investigated for different diets. The rumen microbial cultures included whole rumen fluid, fungi + protozoa, bacteria + protozoa, protozoa and bacteria + fungi and were established by physical and chemical methods. Gas production, short‐chain fatty acid (SCFA) and ammonium production were measured at 24 hr in in vitro incubations using the Hohenheim gas test (HGT) procedure. Seven donor animal diets with different concentrate‐to‐roughage ratios (C:R: 10:90, 30:70, 50:50, 70:30, 70:30BC (BC = NaHCO₃), 90:10 and 90:10BC) and five HGT diets (C:R: 10:90, 30:70, 50:50, 70:30 and 90:10) were formulated. Incubations in the HGT were always based on inoculum from sheep diets with the respective C:R ratio. Gas and ammonium production increased (p < 0.001) as a result of a gradual increase in concentrate proportion of the diets. In general, SCFA production followed the same trend. Whole rumen fluid and bacteria + fungi produced approximately 50% higher gas volume than protozoa and fungi + protozoa fractions, whereas gas production with bacteria + protozoa was at an intermediate level. Coculture of protozoa either with bacteria or with fungi produced more ammonium. Populations without bacteria were characterized by a particularly high acetate/propionate ratio. Although an interaction between microbial group and diet was observed for several variables, no clear direction could be established. Manipulating rumen fluid by selectively suppressing specific rumen microbial groups may be a helpful tool in elucidating their role in nutrient degradation and turnover in vitro.     

Pharmacokinetics of thiamphenicol in Japanese quails (Coturnix japonica) after single intravenous and oral administrations

Thiamphenicol (TP) pharmacokinetics were studied in Japanese quails (Coturnix japonica) following a single intravenous (IV) and oral (PO) administration at 30 mg/kg BW. Concentrations of TP were determined with HPLC and were analyzed by a noncompartmental method. After IV injection, elimination half-life (t_1/2λz), total body clearance (Cl_tot) volume of distribution at steady state (V_dss), and mean residence time (MRT) of TP were 3.83 hr, 0.19 L/hr/kg, 0.84 L/kg, and 4.37 hr, respectively. After oral administration of TP, the peak plasma concentration (C_max) was 19.81 μg/ml and was obtained at 2.00 hr (t_max) postadministration. Elimination half-life (t_1/2λz) and mean absorption time (MAT) were 4.01 hr and 1.56 hr, respectively. The systemic bioavailability following oral administration of TP was 78.10%. TP therapy with an oral dosage of 30 mg/kg BW is suggested for a beneficial clinical effect in quails.     

Sulfadiazine pharmacokinetics in grass carp (Ctenopharyngodon idellus) receiving oral and intravenous administrations

This study aimed to examine the bioavailability (BA) and pharmacokinetic (PK) characteristics of sulfadiazine (SDZ) in grass carp (Ctenopharyngodon idellus) after oral and intravenous administrations. Blood samples were collected at predetermined time points of 0.083, 0.17, 0.5, 1, 2, 4, 8, 16, 24, 48, 72, and 96 hr (n = 6). The samples were extracted and purified by organic reagents and determined by the ultra‐performance liquid chromatography. The software named 3P97 was used to calculate relevant PK parameters. The results demonstrated that the concentration–time profile of SDZ was best described by a one‐compartmental open model with first‐order absorption after a single oral dose. The main PK parameters of the absorption rate constant (K_α), the absorption half‐life (t_{1/2 Kα}), the elimination rate constant (K_e), the elimination half‐life (t_1/2Ke), and the area under concentration–time profile (AUC_0‐∞) were 0.3 1/h, 2.29 hr, 0.039 1/h, 17.64 hr, and 855.78 mg.h/L, respectively. Following intravenous administration, the concentration–time curve fitted to a two‐compartmental open model without absorption. The primary PK parameters of the distribution rate constant (α), the elimination rate constant (β), the distribution half‐life (t_1/2α), the elimination half‐life (t_1/2β), the apparent distribution volume (V_SS), the total clearance (CL), and AUC_0‐∞ were 9.62 1/hr, 0.039 1/hr, 0.072 hr, 17.71 hr, 0.33 L/kg, 0.013 L h^?1 kg^?1, and 386.23 mg.h/L, respectively. Finally, the BA was calculated to be 22.16%. Overall, this study will provide some fundamental information on PK properties in the development of a new formulation SDZ in the future and is partially beneficial for the appropriate usage of SDZ in aquaculture.     

Influence of protein fermentation and carbohydrate source on in vitro methane production

Incubations were carried out with batch cultures of ruminal micro‐organisms from sheep to analyse the influence of the N source on in vitro CH₄ production. The two substrates were mixtures of maize starch and cellulose in proportions of 75:25 and 25:75 (STAR and CEL substrates, respectively), and the three nitrogen (N) sources were ammonia (NH₄Cl), casein (CA) and isolated soya bean protein (SP). Five isonitrogenous treatments were made by replacing non‐protein‐N (NPN) with CA or SP at levels of 0 (NPN), 50 (CA50 and SP50, respectively) and 100% (CA100 and SP100) of total N. All N treatments were applied at a rate of 35 mg of N/g of substrate organic matter and incubations lasted 16.5 h. With both proteins, N source × substrate interactions (p = 0.065 to 0.002) were detected for CH₄ production and CH₄/total VFA ratio. The increases in CH₄ production observed by replacing the NPN with protein‐N were higher (p < 0.05) for STAR than for CEL substrate, but the opposite was observed for the increases in volatile fatty acid (VFA) production. As a consequence, replacing the NPN by increased levels of CA or SP led to linear increases (p < 0.05) in CH₄/total VFA ratio with STAR, whereas CH₄/total VFA ratio tended (p < 0.10) to be decreased with CEL substrate. Increasing the amount of both proteins decreased linearly (p < 0.05) ammonia‐N concentrations, which may indicate an incorporation of amino acids and peptides into microbial protein without being first deaminated into ammonia‐N. In incubations with the tested N sources as the only substrate, the fermentation of 1 mg of CA or SP produced 1.24 and 0.60 μmol of CH₄ respectively. The results indicate the generation of CH₄ from protein fermentation, and that the response of CH₄ production to protein‐N supply may differ with the basal substrate.     

Pharmacokinetics of a single intramuscular injection of cefquinome in buffalo calves

The objective of this study was to investigate the pharmacokinetics of cefquinome following single intramuscular (IM) administration in six healthy male buffalo calves. Cefquinome was administered intramuscularly (2 mg/kg bodyweight) and blood samples were collected prior to drug administration and up to 24 hr after injection. No adverse effects or changes were observed after the IM injection of cefquinome. Plasma concentrations of cefquinome were determined by high‐performance liquid chromatography. The disposition of plasma cefquinome is characterized by a mono‐compartmental open model. The pharmacokinetic parameters after IM administration (mean ± SE) were C_max 6.93 ± 0.58 μg/ml, T_max 0.5 hr, t_½kα 0.16 ± 0.05 hr, t_½β 3.73 ± 0.10 hr, and AUC 28.40 ± 1.30 μg hr/ml after IM administration. A dosage regimen of 2 mg/kg bodyweight at 24‐hr interval following IM injection of cefquinome would maintain the plasma levels required to be effective against the bacterial pathogens with MIC values ≤0.39 μg/ml. The suggested dosage regimen of cefquinome has to be validated in the disease models before recommending for clinical use in buffalo calves.     

Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in alpacas

The aim of this study was to determine the pharmacokinetics and prostaglandin E₂ (PGE₂) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight, adult, female, Huacaya alpacas. A dose of 2.2 mg/kg administered IV and 3.3 mg/kg administered TD using a cross‐over design. Plasma flunixin concentrations were measured by LC‐MS/MS. Prostaglandin E₂ concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE₂ concentrations decreased after IV flunixin meglumine administration but there was minimal change after TD application. Mean t_1/2λz after IV administration was 4.531 hr (range 3.355 to 5.571 hr) resulting from a mean Vz of 570.6 ml/kg (range, 387.3 to 1,142 ml/kg) and plasma clearance of 87.26 ml kg^?1 hr^?1 (range, 55.45–179.3 ml kg^?1 hr^?1). The mean C_max, T_max and t_1/2λz for flunixin following TD administration were 106.4 ng/ml (range, 56.98 to 168.6 ng/ml), 13.57 hr (range, 6.000–34.00 hr) and 24.06 hr (18.63 to 39.5 hr), respectively. The mean bioavailability for TD flunixin was calculated as 25.05%. The mean 80% inhibitory concentration (IC₈₀) of PGE₂ by flunixin meglumine was 0.23 µg/ml (range, 0.01 to 1.38 µg/ml). Poor bioavailability and poor suppression of PGE₂ identified in this study indicate that TD flunixin meglumine administered at 3.3 mg/kg is not recommended for use in alpacas.     

Effect of cellobiose supplementation on in vitro fermentation activity and bacterial numbers of porcine inocula

In this in vitro study, the modified Hohenheim gas test (HGT) was applied to determine fermentation activity and bacterial composition of pig's faecal microbial inoculum using different concentrations of cellobiose. Incubation procedures included normal buffered and osmotic stress conditions (elevated medium salinity). After 24 hr of fermentation, production of gas, ammonia and short‐chain fatty acid (SCFA) was measured, and the gene copy numbers of total bacteria, Lactobacillus spp., Bifidobacterium spp., Roseburia spp., Clostridium Cluster IV spp. and Enterobacteriaceae were analysed using real‐time polymerase chain reaction. There was a significant reduction in gas production after 24 hr when comparing osmotic stress conditions with normal buffered conditions. Under osmotic stress, increasing cellobiose concentrations linearly increased gas production (p < .001), while ammonia, acetic acid and isobutyric acid concentrations decreased (p < .001, p = .012, p = .035 respectively). Under normal buffered conditions, Roseburia spp. gene copies linearly increased with increasing cellobiose concentrations (p = .048). Lactobacillus spp. and Bifidobacterium spp. numbers were higher under osmotic stress (p < .001) compared to normal conditions. Results might point towards a positive impact of cellobiose supplementation on gut health especially under osmotic stress conditions.     

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.     

Preliminary observations on the relationship between gas production and microbial protein synthesis in vitro

The relationship between gas production and microbial protein synthesis was studied in vitro using the method of MENKE et al. (1979). 150 mg starch or cellulose or a mixture of 10% glucose, 40% starch and 50% cellulose was used as the carbohydrate source. The microbial protein synthesis and gas production occurring during 2 hrs after the 5th, 10th, and 23rd hr of incubation were studied. Total and net microbial synthesis were estimated using 32P as a microbial marker and by the net disappearance of NH3-N respectively. The data indicate that the type of carbohydrate and the rate of carbohydrate fermentation influence microbial protein synthesis per unit volume of gas produced. However, the relationship between total synthesis and cumulative gas production (up to 8 hrs incubation) with carbohydrate mixture as the substrate was linear. With reference to these observations, the possibilities and difficulties in using cumulative gas production as an index of microbial growth potential of the feedstuffs are discussed.     

Gas and short‐chain fatty acid production from feeds commonly fed to red deer (Cervus elaphus L.) and incubated with rumen inoculum from red deer and sheep

Efficient red deer supplementary feeding depends on estimations of the nutritive value of offered feeds, frequently estimated with the use of equations derived from domestic ruminants. The aim of this study was to compare the 24‐hour in vitro true dry matter degradability (ivTD₂₄), in vitro gas production (GP) kinetic parameters, GP in 24 hr of incubation (GAS₂₄) and short‐chain fatty acid (SCFA) and microbial biomass (MBS) produced after 24‐hour incubation of feeds in inoculum prepared from sheep and red deer rumen fluid. Eleven feeds, frequently consumed by red deer in Slovenia, which occur either naturally (two fresh grasses, chestnut fruits and common and sessile oak acorns) or are fed as winter supplemental feeds (two grass hays, two grass silages, apple pomace, fresh sugar beetroot), were investigated. The in vitro GP kinetic parameters, GAS₂₄ and ivTD₂₄, did not differ between animal species. Amounts of SCFAs were greater (p < 0.05) when feeds were incubated in sheep inoculum, while molar proportions of acetic and propionic acids did not differ. Molar proportions of butyric acid produced during incubation of high fibre feeds did not differ between animal species, but were higher (p < 0.05) when feeds high in starch or sugar were incubated in red deer inoculum. Greater production of SCFA by sheep rumen microbes suggests better coverage of host animal with energy precursors, while greater production of MBS by red deer rumen microbes suggests better coverage of host animal with protein. Results also suggest that rumens of sheep and red deer are inhabited by different microbial communities, which did not affect the extent of in vitro GP and degradation of feeds used in the present experiment. However, the possibility exists that the divergent nutrient use could be a consequence of different priming by different feeds of the donor animal diets.     

Influence of purified dietary fibre on bacterial protein synthesis in the large intestine of pigs, as measured by the gas production technique

Microbial fermentation of non-digestible carbohydrates in the pig's large intestine induces a shift of N excretion from urea in urine to bacterial protein in faeces. Experiments were carried out to measure the mineral N incorporation by the pig intestinal microflora using 5 purified carbohydrates in a gas-test: starch (S), cellulose (C), inulin (I), pectin (P) and xylan (X). Fermentation kinetics was modelled. N source in the buffer solution was replaced by ¹⁵N labelled NH₄Cl. The bacterial N fixation was determined at mid-fermentation, measuring ¹⁵N incorporation into the solid phase of the buffer. The bacterial N fixation was higher (P < 0.001) with I and S (19.9 and 18.1 mg N/g incubated DM), compared to P, C and X (8.7, 5.9 and 5.5 respectively). Inulin and S were fermented also more rapidly, even if I (0.081 h^− 1) and C (0.074 h^− 1) showed lower half time fractional rate of degradation than S (0.153 h^− 1), P (0.133 h^− 1) and X (0.104 h^− 1). The insoluble dietary fibre content of the substrates was negatively correlated to bacterial N fixation (r = − 0.957, P = 0.011). The high crude protein content of P (32.5 mg g^− 1DM) might explain the lower impact of this substrate on bacterial N fixation, despite its rapid fermentation. Beside the proportion of insoluble fibre, the N content and the rate of fermentation seem to be the major factors influencing bacterial protein synthesis. Further studies including ingredients with variable content of indigestible protein and mean retention time in the pig's intestines are necessary.     

Tilmicosin enteric granules and premix to pigs: Antimicrobial susceptibility testing and comparative pharmacokinetics

The purpose of this study was to compare the pharmacokinetics and relative bioavailability of tilmicosin enteric granules and premix after oral administration at a dose of 40 mg/kg in pigs. Three kinds of different respiratory pathogens were selected for determination of minimal inhibitory concentration (MIC) to tilmicosin. Eight healthy pigs were assigned to a two‐period, randomized crossover design. A modified rapid, sensitive HPLC method was used for determining the concentrations of tilmicosin in plasma. Pharmacokinetic parameters were calculated by using WinNonlin 5.2 software. The MIC₉₀ of tilmicosin against Haemophilus parasuis, Actinbacillus pleuropneumoniae, and Pasteurella multocida were all 8 μg/ml. These results indicated that these common pig respiratory bacteria are sensitive to tilmicosin. The main parameters of time to reach maximum plasma concentration (T_max), elimination half‐life (t_1/2β), mean residence time (MRT), and apparent volume of distribution (V_F) were 2.03 ± 0.37 hr, 29.31 ± 5.56 hr, 25.22 ± 2.57 hr, 4.06 ± 1.04 L/kg, and 3.05 ± 0.08 hr, 17.06 ± 1.77 hr, 15.55 ± 1.37 hr, 2.95 ± 0.62 L/kg after the orally administrated tilmicosin enteric granules and premix. The relative bioavailability of tilmicosin enteric granules to premix was 114.97 ± 7.19%, according to the AUC_0‐t values. These results demonstrated that tilmicosin enteric granules produced faster tilmicosin absorption, slower elimination, larger tissue distribution, and higher bioavailability compared to the tilmicosin premix. The present study results manifest that tilmicosin enteric granules can be used as a therapeutic alternative to premix in clinical treatment.     

Pharmacokinetics of sanguinarine,chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half‐life (t_1/2) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (C_max) of DHSA (2.49 ± 1.4 μg/L) was higher that of SA (1.89 ± 0.8 μg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h^?1·kg^?1) with a t_1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.     

Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection

The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4 kg. Each dog received either intravenous or subcutaneous injection, both at 5 mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t_1/2λz) was calculated as 7.40 ± 0.79 and 7.91 ± 1.53 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (V_SS) were determined as 39.91 ± 4.04 ml hr⁻¹ kg⁻¹ and 345.71 ± 28.66 ml/kg, respectively. After subcutaneous injection, the peak concentration (C_max; 10.50 ± 0.22 μg/ml) was observed at 3.2 ± 1.1 hr, and the absorption half-life (t_1/2ka) and absolute bioavailability (F) were calculated as 0.74 ± 0.23 hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T > MIC) values calculated here, an intravenous or subcutaneous dose at 5 mg/kg of ceftiofur sodium once every 12 hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0 μg/ml.     

Pharmacokinetics of harpagoside in horses after intragastric administration of a Devil's claw (Harpagophytum procumbens) extract

Devil's claw is used for the treatment of inflammatory symptoms and degenerative disorders in horses since many years, but without the substantive pharmacokinetic data. The pharmacokinetic parameters of harpagoside, the main active constituent of Harpagophytum procumbens DC ex Meisn., were evaluated in equine plasma after administration of Harpagophytum extract FB 8858 in an open, single‐dose, two‐treatment, two‐period, randomized cross‐over design. Six horses received a single dose of Harpagophytum extract, corresponding to 5 mg/kg BM harpagoside, and after 7 days washout period, 10 mg/kg BM harpagoside via nasogastric tube. Plasma samples at certain time points (before and 0–24 hr after administration) were collected, cleaned up by solid‐phase extraction, and harpagoside concentrations were determined by LC‐MS/MS using apigenin‐7‐glucoside as internal standard. Plasma concentration‐time data and relevant parameters were described by noncompartmental model through PKSolver software. Harpagoside could be detected up to 9 hr after administration. C_max was found at 25.59 and 55.46 ng/ml, t_1/2 at 2.53 and 2.32 hr, respectively, and t_max at 1 hr in both trials. AUC_0–inf was 70.46 and 117.85 ng hr ml^?1, respectively. A proportional relationship between dose, C_max and AUC was observed. Distribution (V_z/F) was 259.04 and 283.83 L/kg and clearance (CL/F) 70.96 and 84.86 L hr^?1 kg^?1, respectively. Treatment of horses with Harpagophytum extract did not cause any clinically detectable side effects.     

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus) at three temperatures after one single intramuscular injection

The pharmacokinetic profiles of florfenicol (FF) or florfenicol amine (FFA) in crucian carp were compared at different water temperatures after single intramuscular administration of FF at 10 mg/kg bodyweight. The concentrations of FF and FFA were determined by a high‐performance liquid chromatography method, and then, the concentration versus time data were subjected to compartmental analysis using a one‐compartment open model. At the water temperatures of 10, 20, and 25°C, the peak concentrations (C_maxs) of FF were 2.28, 2.29, and 2.34 μg/ml, respectively, while those of FFA were 0.42, 0.71, and 0.82 μg/ml, respectively. And the absorption half‐life (t_1/2ka) of FF was 0.21, 0.19, and 0.21 hr, while the elimination half‐life (t_1/2kel) was 31.66, 24.77, and 21.48 hr, respectively. For FFA, the formation half‐life (t_1/2kf) was 3.85, 8.97, and 12.43 hr, while the t_1/2kel was 58.34, 30.27, and 21.22 hr, respectively. The results presented here demonstrated that the water temperature had effects on the elimination of both FF and FFA and the formation of FFA. Based on the T > MIC values calculated here, to treat the infections of bacterial with MIC value ≤ 0.5 μg/ml, FF intramuscularly given at 10 mg/kg bodyweight with a 72‐hr interval is sufficient at the water temperature of 10°C, while the intervals of 60 and 48 hr were needed at 20 and 25°C, respectively. But to treat bacterial with higher MIC values, more FF or FF at 10 mg/kg BW but with shorter intervals should be intramuscularly given to the infected fish.     

Pharmacokinetics of imidocarb dipropionate in white-tailed deer (Odocoileus virginianus) after single intramuscular administration

This study was designed to investigate the pharmacokinetics of imidocarb, a carbanilide derivative, in white-tailed deer (Odocoileus virginianus). The pharmacokinetic properties of a single intramuscular (IM) dose of imidocarb were determined in 10 deer. A single IM injection of 3.0 mg/kg imidocarb dipropionate was administered, and blood samples were collected prior to, and up to 48 hr after imidocarb administration. Plasma imidocarb concentrations were determined by high-performance liquid chromatography with ultraviolet detection. The disposition of plasma imidocarb was best characterized by a two-compartment open model. The mean ± SE maximal imidocarb concentration in deer was 880.78 ± 81.12 ng/ml at 38.63 ± 5.30 min postinjection. The distribution phase had a half-life (t_1/2α) of 25.90 ± 10.21 min, and plasma imidocarb concentration declined with a terminal elimination half-life (t_1/2β) of 464.06 ± 104.08 min (7.73 ± 1.73 hr). Apparent volume of distribution based on the terminal phase (V_Z/F) was 9.20 ± 2.70 L/kg, and apparent total body clearance (Cl/F) was 15.97 ± 1.28 ml min⁻¹ kg⁻¹.     

Adaptation of healthy adult cats to select dietary fibers in vivo affects gas and short-chain fatty acid production from fiber fermentation in vitro

Nine young adult (1.73 ± 0.03 yr) male cats were used to determine the effects of microbial adaptation to select dietary fiber sources on changes in pH in vitro and on total and hydrogen gas, short-chain fatty acid (SCFA), and branched-chain fatty acid (BCFA) production. Cats were adapted to diets containing 4% cellulose, fructooligosaccharides (FOS), or pectin for 30 d before fecal sampling. Each cat was used as a single donor, and fecal inoculum was reacted with each of the aforementioned fiber substrates. Adaptation to dietary FOS resulted in a greater change in pH when exposed to FOS than pectin (adaptation × substrate, P < 0.001). When exposed to the FOS substrate, adaptation to dietary FOS or pectin increased hydrogen gas production (adaptation × substrate, P = 0.021). Adaptation to dietary FOS increased acetate and total SCFA production when exposed to FOS substrate in vitro (adaptation × substrate, P = 0.001). When exposed to the FOS substrate, propionate production tended to increase with adaptation to dietary cellulose (adaptation × substrate, P = 0.060). The BCFA + valerate tended to decrease with adaptation to dietary FOS when exposed to FOS substrate in vitro (adaptation × substrate, P = 0.092). Fructooligosaccharides resulted in the greatest change in pH and production of total gas (P < 0.001), hydrogen gas (P < 0.001), acetate (P < 0.001), propionate (P < 0.001), butyrate (P < 0.001), total SCFA (P < 0.001), and total BCFA + valerate production (P < 0.001). Adaptation to the FOS or pectin diet increased production of hydrogen gas with FOS and pectin substrates. Adaptation to pectin increased (P = 0.033) total gas production with FOS and pectin substrates. Overall, adaptation to either FOS or pectin led to greater SCFA and gas production, but adaptation to FOS resulted in the greatest effect overall.     

Pharmacokinetics and relative bioavailability of meloxicam oil suspension in pigs after intramuscular administration

This study aimed to develop one novel meloxicam (MEL) oil suspension for sustained-release and compare the pharmacokinetic characteristics of it with MEL conventional formulation in pigs after a single intramuscular administration. Six healthy pigs were used for the study by a crossover design in two periods with a withdrawal interval of 14 days. Plasma concentrations of MEL were measured by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetic parameters were calculated by noncompartmental methods. The difference was statistically significant (p < .05) between MEL oil suspension and MEL conventional formulation in pharmacokinetic parameters of mean residence time (6.16 ± 4.04) hr versus (2.66 ± 0.55) hr, peak plasma concentration (C_max) (0.82 ± 0.12) µg/ml versus (1.12 ± 0.22) µg/ml, time needed to reach C_max (T_max) (2.33 ± 0.82) hr versus (0.59 ± 0.18) hr, and terminal elimination half-life (t_1/2λz) (3.74 ± 2.66) hr versus (1.55 ± 0.37) hr. The mean area under the concentration–time curve (AUC_0–∝) of MEL oil suspension and MEL conventional formulation was 5.35 and 3.43 hr µg/ml, respectively, with a relative bioavailability of 155.98%. Results of the present study demonstrated that the MEL oil suspension could prolong the effective time of drugs in blood, thereby reducing the frequency of administration on a course of treatment. Therefore, the novel MEL oil suspension seems to be of great value in veterinary clinical application.     

Pharmacokinetics of enrofloxacin and danofloxacin in premature calves

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty‐four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR‐IV (10 mg/kg, IV), ENR‐IM (10 mg/kg, IM), DNX‐IV (8 mg/kg, IV), and DNX‐IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high‐pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half‐life (t_1/2λz) 11.16 and 17.47 hr, area under the plasma concentration–time curve (AUC_0‐48) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady‐state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr^?1 kg^?1, respectively. The PK parameters of ENR and DNX following IM injection were t_1/2λz 21.10 and 28.41 hr, AUC_0‐48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC_0‐48CPR/AUC_0‐48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC_0‐24/minimum inhibitory concentration (MIC) and maximum concentration (C_max)/MIC ratios for susceptible bacteria, with the MIC₉₀ of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.