Pharmacokinetics of levamisole after intramuscular and oral administrations to Caspian salmon (Salmo trutta caspius)

The pharmacokinetic parameters of levamisole were determined in the Caspian salmon after intramuscular (IM), oral by gavage, and oral by feed administrations. Eighty-one healthy fish in three different groups received levamisole at the dose of 25 mg/fish by each route. Blood samples were collected at time points of 0, 0.5, 1, 2, 4, 6, 12, 14, and 24 hr after administrations. Plasma levamisole concentrations were measured by a validated high-performance liquid chromatography (HPLC) assay and were analyzed using a noncompartmental approach. The mean terminal half-life was 4.56, 3.95, and 2.91 hr for IM, gavage and feed routes, respectively. The peak plasma concentration for IM, gavage, and feed routes of levamisole were 35.53, 4.63, and 8.36 µg/ml, respectively, at the time of 0.25 for IM, and 1 hr for gavage and feed. The relative bioavailability for gavage and feed routes was 54.80 and 69.30. The similar bioavailability for gavage and feed might be indicative of similar efficacy for these routes of administrations. Further studies are warranted to evaluate the absolute oral bioavailability and the effective dose in Caspian salmon.     

Sulfadimethoxine in giant freshwater prawns (Macrobrachium rosenbergii): an attempt to estimate the withdrawal time by a population pharmacokinetic approach

The fates of sulfadimethoxine (SDM) for different routes of administration were investigated in muscle tissue of giant freshwater prawns, Macrobrachium rosenbergii, following either intramuscular (i.m.) or gavage administration at a dosage of 50 mg/kg body weight (b.w.). The depletion patterns of SDM were also examined after medicated feed treatment at the feeding concentration of 10 g/kg of feed twice a day at a rate of 1% of total b.w. for five consecutive days. The concentration of SDM in prawn muscle tissue was measured using a high‐performance liquid chromatography (HPLC) equipped with ultraviolet detector. Noncompartmental analyses were used to estimate basic pharmacokinetic parameters for the i.m. and gavage data, while a population model was developed to analyze the entire data set including the feed group. Using the Monte Carlo simulations, the withdrawal times (WT) for the orally administered SDM in feed supplement were determined. Maximum concentration of SDM was significantly higher in the i.m. than in the gavage group, and the area under the curve (AUC) value for relative bioavailability following gavage administration was 25.6%. Using Monte Carlo simulation, for a maximum residue limit (MRL) of 0.1 μg/g, the WT for muscle after oral administration of SDM in feed was estimated to be 67 h, while for a MRL of 0.2 μg/g, the WT was estimated to be of 54 h.     

Effect of super dosing of phytase on growth performance,ileal digestibility and bone characteristics in broilers fed corn–soya‐based diets

A feeding trial was designed to assess the effect of super dosing of phytase in corn–soya‐based diets of broiler chicken. One hundred and sixty‐eight day‐old broilers were selected and randomly allocated to four dietary treatment groups, with 6 replicates having 7 chicks per treatment group. Two‐phased diets were used. The starter and finisher diet was fed from 0 to 3 weeks and 4 to 5 weeks of age respectively. The dietary treatments were consisted of normal phosphorus (NP) group without any phytase enzyme (4.5 g/kg available/non‐phytin phosphorus (P) during starter and 4.0 g/kg during finisher phase), three low‐phosphorus (LP) groups (3.2 g/kg available/non‐phytin P during starter and 2.8 g/kg during finisher phase) supplemented with phytase at 500, 2500, 5000 FTU/kg diet, respectively, to full fill their phosphorus requirements. The results showed that super doses of phytase (at 2500 FTU and 5000 FTU/kg) on low‐phosphorus diet improved feed intake, body weight gain, ileal digestibility (serine, aspartic acid, calcium, phosphorus), blood P levels and bone minerals such as calcium (Ca), P, magnesium (Mg) and zinc (Zn) content. It could be concluded that super doses of phytase in low‐phosphorus diet were beneficial than the normal standard dose (at 500 FTU/kg) of phytase in diet of broiler chicken.     

Pharmacokinetics of thymoquinone in layer chickens following oral and intravenous administration

Thymoquinone (TQ) is the major constituent of Nigella sativa and known to possess a variety of pharmacological effects. This study was designed to evaluate the pharmacokinetic profile of TQ following oral (PO) and intravenous (IV) administration in layer chickens. The layer chickens were equally divided into two groups (six chickens in each group, total 12 chickens), and TQ was administered via PO and IV routes. For PO route, the dose was 20 mg/kg b.w. and for IV route, 5 mg/kg b.w. was administered, respectively. A sensitive and accurate High‐Performance Liquid Chromatography (HPLC) technique was validated for the quantification of TQ from plasma. The limit of detection (LOD) and limit of quantification (LOQ) were 0.02 µg/ml and 0.05 µg/ml, respectively with >80% recovery. Maximum plasma concentration (C_max) following PO and IV administration was 8.805 and 4.497 µg/ml, respectively, while time to reach at maximum concentration (T_max) was 1 and 0.1 hr, respectively. The elimination half‐lives were recorded as 1.02 and 0.978 hr, whereas the mean residence times were 1.79 and 1.036 hr following both PO and IV administration, respectively. The 85% PO bioavailability was indicative that TQ could be used for various therapeutic purposes in layer chickens.     

Study on the abuse of amantadine in tissues of broiler chickens by HPLC‐MS/MS

To evaluate the residual target tissues for better monitoring of amantadine abuse in broiler chickens, 22‐day‐old commercial Arbor Acres broiler chickens were, respectively, fed with 10, 20, and 40 mg/kg of amantadine for five consecutive days. Plasma, breast, and liver tissue samples from the chickens were collected 0, 4, 16, 24, 48, 96, 144, and 312 h after amantadine withdrawal. The high‐performance liquid chromatography–tandem mass spectrometry method was used to detect the concentrations of amantadine. The highest concentration was found in the chicken liver and it took the longest time for amantadine to vanish by metabolism. In the high‐dose group, amantadine residues were still detected 312 h after amantadine withdrawal. As the amantadine dose increased, amantadine residues in the chicken liver were more slowly to disappear than in other tissues. Even if approximately the same concentration of amantadine residues was found in chicken breast and plasma samples, it took a shorter time before the residues were eliminated. In the medium‐ and high‐dose groups, the concentrations of amantadine residues in chicken liver samples were substantially higher than those in chicken breast and plasma samples, and it took more time to eliminate them. Therefore, the chicken liver can be used as a target tissue to detect illegal use of amantadine.     

Effect of laboratory‐isolated Lactobacillus plantarum LGFCP4 from gastrointestinal tract of guinea fowl on growth performance,carcass traits,intestinal histomorphometry and gastrointestinal microflora population in broiler chicken

The study aimed to investigate the effect of feed supplements, viz Lactobacillus plantarum LGFCP4 (laboratory isolate from GIT of Guinea fowl), Lactobacillus acidophilus (NCDC, Karnal) and in‐feed antibiotic bacitracin methylene disalicylate (BMD) on growth performance, FCR, carcass traits and immune organs weight, intestinal histomorphometry and gastrointestinal microflora population in broiler chickens. In a completely randomized design, CARIBRO‐Dhanraja broiler chicks (n = 160) were used with four treatment groups. During the entire experimental duration of 35 days, treatment groups were provided with different dietary treatments (T1 – basal diet (negative control), T2 – antibiotic growth promoter BMD 20 g/100 kg feed (positive control), T3 – 1 × 10⁸ cfu of L. acidophilus/gm‐fermented feed +MOS 1 g/kg feed and T4 – 1 × 10⁸ cfu of laboratory‐isolated L. plantarum LGFCP4/gm‐fermented feed+ MOS 1 g/kg feed. After 35 days of experimental period, no significant results have been observed in different growth performance traits among treatment groups. Cut‐up parts and edible organs' weight remained unaffected by dietary supplementation, whereas weight of immune organs were significantly higher (p < 0.05) in L. plantarum LGFCP4‐supplemented group. At the end of feeding trial, significantly (p < 0.05) lower E. coli count was observed in crop of T4 birds, while in ileum, T2 and T3 showed lower count. In caeca, T2 group showed lowest E. coli count. Salmonella count in crop and ileum was significantly (p < 0.05) low in T3 and T4, while in caeca, T2 group showed lowest count. In terms of histomorphometry, duodenal villous height (VH), crypt depth (CD) and VH:CD ratio were higher for T3 and T4 and lowest values were obtained for T2 group. The results of the study showed that L. plantarum LGFCP4 isolated from GIT of guinea fowl can effectively replace in‐feed antibiotic growth promoters in broiler diets by altering intestinal villi morphology and improving the gut health by reducing the pathogenic microbial load.     

Evaluation of the protective effect of lycopene on growth performance,intestinal morphology,and digestive enzyme activities of aflatoxinB1 challenged broilers

The current study was conducted to investigate the protective efficiency of dietary lycopene (LYC) supplementation on growth performance, intestinal morphology, and digestive enzyme activities aflatoxinB₁ (AFB₁) challenged broilers. A total of 240 days old Arber across male broiler chicks were randomly allocated in five treatments and six replicates (eight birds per replicate); feed and water were provided ad libitum during the 42 days experiment. The treatment diets were as follows: (i) Basal diet (control), (ii) Basal diet + 100 µg/kg AFB₁ contaminated diet, (iii) Basal diet + 100 µg/kg AFB₁ + 100 mg/kg LYC1, (iv) Basal diet + 100 µg/kg AFB₁ + 200 mg/kg LYC2, and (v) Basal diet + 100 µg/kg AFB₁ + 400 mg/kg LYC3. The results showed that the addition of LYC to AFB₁ contaminated broiler diets significantly increased (p < .05) average daily gain (ADG) and decreased feed conversion ratio (FCR) compared to the AFB₁ diet. AFB₁ diet decreased the intestinal villus height (VH) and crypt depth ratio (VCR) while increasing the crypt depth (CD). However, dietary LYC supplemented diets relieved the intestinal morphological alterations. Dietary LYC supplementation (200 and 400 mg/kg) significantly improved (p < .05) intestinal digestive enzyme amylase and lipase activities with AFB₁ contaminated diet. These findings suggested that LYC is a promising feed supplement in the broiler industry, alleviating the harmful effects of AFB₁.     

Pharmacokinetics of deflazacort in rabbits after intravenous and oral administration and its interaction with erythromycin

The pharmacokinetic of deflazacort after intravenous and oral administration and the effect of erythromycin on the disposition of deflazacort in rabbits were investigated. A parallel study was carried out in twelve rabbits. The plasma concentration–time profiles of deflazacort were determined after intravenous and oral administration of single dosages of 5 mg/kg in the presence and absence (baseline) of multiple dose erythromycin regimens. Plasma concentrations of 21‐desacetyldeflazacort were determined by HPLC. Plasma concentration–time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The t_½λz values following intravenous and oral administration were 3.67 and 4.96 hr, respectively. The apparent volume of distribution at steady‐state (V_ss) was 4.08 ± 0.31 L/kg, this value indicates that deflazacort is widely distributed into the extravascular tissues. Moreover, bioavailability after oral administration of deflazacort (F = 87.48%) was high. Pharmacokinetic analysis after both routes of administration revealed a significant reduction in total body clearance, a significant increase in mean residence time, half‐life and plasma concentrations of the steroid in the presence of multiple dose erythromycin. The results indicated the influence of the erythromycin on deflazacort disposition, which is consistent with a pharmacokinetic‐type interaction in the elimination of the drug from the body. Moreover, this interaction should be considered to avoid adverse effects when using both drugs concomitantly.     

Pharmacokinetics of sodium baicalin following intravenous and intramuscular administration to piglets

The purpose of this study was to determine the pharmacokinetics of baicalin after intravenous and intramuscular administration of sodium baicalin at 50 mg/kg to piglets. Plasma baicalin levels were determined by high‐performance liquid chromatography. The plasma concentration–time data of baicalin for both administration routes were best described by two‐compartmental open model. The area under the plasma concentration–time curve and the elimination half‐lives were 77.47 ± 6.14 µg/ml × h and 1.73 ± 0.16 hr for intravenous and 64.85 ± 5.67 µg/ml × h and 2.42 ± 0.15 hr for intramuscular administration, respectively. The apparent volume of distribution and body clearance were 1.63 ± 0.23 L/kg and 2.74 ± 0.30 L h^?1 kg^?1 for intravenous and 0.51 ± 0.10 L/kg and 0.78 ± 0.08 L h^?1 kg^?1 for intramuscular routes, respectively. An intramuscular injection of sodium baicalin in piglets resulted in rapid and complete absorption, with a mean maximal plasma concentration of 77.28 ± 7.40 µg/ml at 0.17 hr and a high absolute bioavailability of 83.73 ± 5.53%.     

Whole pearl millet feeding does not impair performance and nutrient digestibility in 28-day-old broiler chickens

The effects of varying inclusion levels of whole grain millet in millet–soya bean-based diets on growth performance, gizzard development, digesta characteristics and nutrient digestion in broiler chicken were investigated. Starter (0–14 days) and grower (15–28 days) broiler chicken diets containing pearl millet at 500 and 540 g/kg diet, respectively, were formulated. The diets comprised of 0%, 20%, 40%, 60%, 80% and 100% of millet incorporated as whole grain. One-day-old unsexed Arbor Acres Plus chicks (n = 540) were allotted to the experimental diets in a completely randomized design with the diets and water provided ad libitum for 28 days. Each treatment was replicated seven times, and each replicate had 12 chicks. Results showed that daily live weight gain and feed conversion ratio of chickens on the whole millet grain diets compared favourably with chicken on the control in both starter and grower phases, while feed intake reduced quadratically (p < .05) with increased whole grain millet levels in the starter phase. Morphological and structural characteristics of the gizzard and small intestine and intestinal digesta pH and viscosity were also unaffected (p > .05) by whole grain millet inclusion levels. However, the weight of intact millet grain in gizzard increased linearly (p < .001) with whole grain millet inclusion in the diets. Dietary whole grain millet inclusion also consistently lowered (p < .05) jejunal and ileal maltase and sucrase activities, but did not influence (p > .05) pancreatic amylase activity. Ileal crude protein and starch digestibility increased, while ileal energy digestibility decreased significantly (p < .05) with whole grain millet inclusion. Whole grain millet inclusion in broiler starter and grower diets up to 500–540 g/kg did not negatively impact on broiler chicken performance.     

Pharmacokinetics of procaterol in thoroughbred horses

Procaterol (PCR) is a beta‐2‐adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography–mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady‐state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half‐life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.     

Black soldier fly and yellow mealworm live larvae for broiler chickens: Effects on bird performance and health status

The commercial broiler chicken strains are the result of successful selection programmes. Most of the problems related to welfare arise from the high growth rate and body weight. The use of environmental enrichments in intensive farming could have a positive effect on birds by increasing animal welfare. The aim of the study was to evaluate the effects of Hermetia illucens (HI) and Tenebrio molitor (TM) live larvae in the diets of broiler chickens on growth performance, carcass yield and health status. A total of 180 four-day-old male broiler chickens (Ross 308) were randomly allotted to 18 pens. Each pen was assigned to one of the three dietary treatments (6 replicates/treatment, 10 birds/replicate) as follows: (i) control diet (C): commercial feed (two feeding phases: starter [4–11 days] and grower [12–38 days]), (ii) HI: C + 5% of the expected daily feed intake (DFI) HI live larvae (calculated on dry matter [DM]) and (iii) TM: C + 5% of DFI TM live larvae (DM). At 39 days of age, birds were slaughtered. Growth performance parameters were overall not affected by dietary treatments, except for the grower phase feed conversion ratio (FCR) and the overall FCR being better in the TM broilers than the others (p < 0.01). No differences were observed for slaughtering performance and haematological and serum parameters, except for the spleen relative weight being higher (p < 0.01) in the birds administered with larvae when compared to the C group. Gut morphometric indexes and histopathological alterations were not influenced by insect larvae administration. In conclusion, the administration in limited quantities of HI and TM live larvae as environmental enrichment has no negative effects on broiler chicken growth performance and health status. A behavioural study could confirm that live insect larvae represent a novel natural environmental enrichment in broiler farming.     

Response of in ovo administration of zinc on egg hatchability and immune response of commercial broiler chicken

An experiment was conducted to determine the effect of in ovo administration of different forms of zinc with respect to hatchability and performance of commercial broiler chicken. In trial 1, the fertile eggs on day 18 were divided into six treatment groups: Group I as control without any supplementation of zinc, group II to IV were supplemented with 0.5 mg zinc per egg as zinc sulphate, zinc methionine or nano zinc, respectively, and Group V with nano zinc at 0.25 mg zinc per egg. Sixth group received 0.5 ml citric acid per egg as sham control. The results of the first trial indicated that in ovo administration of nano zinc at both levels and zinc methionine resulted in complete failure of hatchability. A second trial to validate the result of trial 1 consisted of Group I control (no administration). Group II and Group III were supplemented with zinc sulphate and zinc methionine, respectively, at 0.5 mg zinc per egg. Group IV and Group V were supplemented with nano zinc at 0.04 and 0.08 mg per egg. In the second trial, again there was a similar pattern for zinc sulphate and zinc methionine. Administration of Zn by nano form had around 80% hatchability on fertile eggs in comparison with the unadministered control eggs (92%). There was no difference (p > .05) in body weight gain, feed intake and FCR. No difference (p > .05) was observed between treatments for cell‐mediated immune response and humoral immune response. Nano Zn‐administered group showed a non‐significant downregulation of MUC2 gene. It could be concluded that in ovo administration of higher levels of zinc has to be with caution for the developing embryo of commercial broiler chicken.     

Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration

The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (T_max) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.     

Effect of different levels of copper nanoparticles and copper sulphate on performance,metabolism and blood biochemical profiles in broiler chicken

A study was conducted to investigate the influence of copper administration in ovo to chicken embryos and/or supplied in drinking water to growing chickens in the form copper nanoparticles (Cu‐NP) or copper sulphate (CuSO₄). The fertilised eggs were assigned to three groups (n = 50 per group): control (not injected), injected with 50 mg/kg Cu‐NP or with 50 mg/kg CuSO₄ at day 1 of incubation. Thereafter, 126 one‐day‐old broiler chickens were randomly assigned to seven post‐hatched groups: control not injected and not provided with Cu in the drinking water, injected with 50 mg/kg Cu‐NP + 20 mg/kg in water, not injected + 20 mg/kg Cu‐NP in water, injected with 50 mg/kg CuSO₄ + 20 mg/kg in water, not injected + 20 mg/kg CuSO₄ in water, injected with 50 mg/kg Cu‐NP and injected with 50 mg/kg CuSO₄. The experiment was carried out from day 1 to 35 post‐hatching. The in ovo injection of Cu improved the final body weight, average daily gain and feed conversion ratio in relation to the control group. Conversely, the provision of Cu in the drinking water had less of an effect on growth performance in comparison with the injected groups. A significant improvement was shown in energy and nitrogen utilisation, being better for Cu‐NP than CuSO₄. The cholesterol, urea and glucose levels in the blood were reduced by Cu‐NP treatment in relation to the other groups. The relative weight of the liver was decreased, while bursa of Fabricius was increased in Cu groups in relation to the control group. Cu excretion was only reduced in chickens injected with 50 mg/kg Cu‐NP + 20 mg/kg in water. The immune‐related genes were not affected by the treatments. The in ovo injection of Cu‐NP might improve broiler performance more efficiently than the injection of CuSO₄ or the provision of Cu‐NP and/or CuSO₄ in drinking water.     

Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses

The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half‐life, volume of distribution at steady‐state, and clearance after IV administration for plasma samples were 0.78 ± 0.176 hr, 136.1 ± 19.69 ml/kg, and 165.2 ± 29.72 ml hr^‐1 kg^?1, respectively. Meropenem in synovial fluid had a slower elimination than plasma with a terminal half‐life of 2.4 ± 1.16 hr. Plasma protein binding was estimated at 11%. Based on a 3‐compartment open pharmacokinetic model of simultaneously fit plasma and synovial fluid, dosage simulations were performed. An intermittent dosage of meropenem at 5 mg/kg IV every 8 hr or a constant rate IV infusion at 0.5 mg/kg per hour should maintain adequate time above the MIC target of 1 μg/ml. Carbapenems are antibiotics of last resort in humans and should only be used in horses when no other antimicrobial would likely be effective.     

Use of blends of organic acids and oregano extracts in feed and water of broiler chickens to controlSalmonella Enteritidis persistence in the crop and ceca of experimentally infected birds

The aim of the present evaluation was to assess the efficacy of blends of organic acids and oregano extracts supplied from d 1 to 21 and from d 35 to 42 in feed, drinking water, or both, in controllingSalmonella Enteritidis persistence in the crop and ceca of broiler chicken. A total of 105 one-day-old male broiler breeder chicks were randomly distributed into 5 different treatments according to the supply of referred blends andSalmonella Enteritidis challenge.Salmonella Enteritidis was inoculated directly in the crop of birds at the 15 d of age. Treatments were unsupplemented unchallenged, unsupplemented challenged, supplemented through water and challenged, supplemented through feed and challenged, and supplemented through feed and water and challenged. Use of the additives in feed and water and in water alone efficiently controlledSalmonella shedding and reduced cecal persistence. Immune mechanisms involved are proposed.     

Pharmacokinetics of valnemulin after intravenous,intramuscular, and oral administration in layer chickens

The pharmacokinetic characteristics of valnemulin in layer chickens were studied after single intravenous, intramuscular, and oral administration at a dose of 15 mg/kg body weight. Plasma samples at certain time points were collected and the drug concentrations in them by ultra high‐performance liquid chromatography tandem mass spectrometry (UHPLC‐MS). The concentration–time data for each individual were plotted by noncompartmental analysis for the whole three routes. Following intravenous administration, the plasma concentration showed tiny fluctuation. The elimination half‐life (), total body clearance (Cl), and area under the plasma concentration–time curve (AUC) were 1.85 ± 0.43 h, 2.2 ± 0.9 L/h, and 7.52 ± 2.46 μg·h/mL, respectively. Following intramuscular administration, the peak concentration (C_max, 1.40 ± 0.43 μg/mL) was achieved at the time of 0.34 h. A multiple‐peak phenomenon existed after oral administration, and the first peak and secondary peak were at 10 min and during 2–4 h, respectively, while the tertiary peak appeared during 5–15 h. The bioavailability (F %) for intramuscular and oral administration was 68.60% and 52.64%, respectively. In present study, the detailed pharmacokinetic profiles showed that this drug is widely distributed and rapidly eliminated, however has a low bioavailability, indicating that valnemulin is likely to be a favorable choice in the clinical practice.     

Assessment of the long‐acting ivermectin formulation in sheep: Further insight into potential pharmacokinetic interactions

The aim of the current study was to evaluate the in vivo pharmacokinetic of ivermectin (IVM) after the administration of a long‐acting (LA) formulation to sheep and its impact on potential drug‐drug interactions. The work included the evaluation of the comparative plasma profiles of IVM administered at a single therapeutic dose (200 μg/kg) and as LA formulation at 630 μg/kg. Additionally, IVM was measured in different gastrointestinal tissues at 15 days posttreatment with both IVM formulations. The impact of the long‐lasting and enhanced IVM exposure on the disposition kinetics of abamectin (ABM) was also assessed. Plasma (IVM and ABM) and gastrointestinal (IVM) concentrations were analyzed by HPLC with fluorescent detection. In plasma, the calculated C_max and AUC_0‐t values of the IVM‐LA formulation were 1.47‐ and 3.35‐fold higher compared with IVM 1% formulation, respectively. The T_1/2ab and T_max collected after administration of the LA formulation were 2‐ and 3.5‐fold longer than those observed after administration of IVM 1% formulation, respectively. Significantly higher IVM concentrations were measured in the intestine mucosal tissues and luminal contents with the LA formulation, and in the liver, the increase was 7‐fold higher than conventional formulation. There was no drug interaction between IVM and ABM after the single administration of ABM at 15 days post‐administration of the IVM LA formulation. The characterization of the kinetic behavior of the LA formulation to sheep and its potential influence on drug‐drug interactions is a further contribution to the field.     

Preliminary clinical pharmacological investigations of tylosin and tiamulin in chickens

Summary

The minimal inhibitory concentrations (M1C) of tiamulin and tylosin for mycoplasma. Gram‐positive, and Gram‐negative micro‐organisms isolated from chickens were determinated by the agar dilution method. Median M1C values for tiamulin against Mycoplasma gallisepticum (0.05 μg/ml) and Mycoplasma synoviae (0.10 μg/ml) were 2 to 4 times lower than the corresponding values for tylosin. Tiamulin was also slightly more effective in vitro in inhibiting Escherichia coli, Pasteurella multocida, and beta‐haemolytic streptococci than was tylosin. Groups of chicken were offered tiamulin medicated drinking water at rates of 125 and 250 mg/litre for 48 hours. Average serum tiamulin concentrations were 0.38 and 0.78 μg/ml, respectively. When tylosin tartrate was added to the drinking water at 500 and 700 mg/litre, average serum drug levels were 0.12 and 0.17 μg/ml, respectively.

Tiamulin was 45% bound in chicken serum, as against 30% serum protein binding or tylosin. Correlations were made between free (non protein bound) serum drug levels and the MIC values of the two drugs. Such comparisons suggest that when tiamulin is given in the drinking water at rates of 125 to 250 mg/litre, better antimycoplasmal activity is to be expected in vivo than by giving tylosin tartrate in the drinking water at 500 to 700 mg/litre. Based on these data, no clinical efficacy of these dose rates can be expected in flocks infected by gram‐negative microorganisms such as E. coli or P. multocida. The tylosin tartrate rate of 500 to 700 mg/litre, may be clinical ineffective the treatment of Staphylococcus aureus infections.