Pharmacokinetics of tapentadol in laying hens and its residues in eggs after multiple oral dose administration

1. The aim of the study was to evaluate the pharmacokinetics (PKs) of tapentadol (TAP), a novel opioid analgesic, in laying hens after intravenous (IV) and oral (PO) administration and to quantify the concentrations of TAP residues in eggs.

2. Twenty healthy laying hens were divided into three groups: A (n = 6), B (n = 6) and C (n = 8). The study was conducted in two phases. Groups A and B received TAP by IV and PO routes at the dose of 1 and 5 mg/kg, respectively.

3. No visible adverse effects were observed after administration of the drug. TAP plasma concentrations were detectable up to 4 h following administration. Following IV administration, TAP plasma concentrations were only higher than the minimal effective concentration (148 ng/ml) reported for humans for 1 h. After single PO administration, plasma concentrations of TAP would not conform to software algorithms and the PK parameters were not calculated. TAP concentration following multiple PO doses at 5 mg/kg for 5 d was found to be higher and more persistent (12 h vs. 7 h) in yolk compared with albumen.

4. This is the first PK study on the novel atypical opioid TAP in laying hens. Further studies are required to investigate the analgesic efficacy and actual effective plasma concentration of TAP in this species.     

Pharmacokinetics of meloxicam in adult goats: a comparative study of subcutaneous,oral and intravenous administration

AIMS: To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5?mg/kg bodyweight.

METHODS: Five healthy Saanen goats, aged 12–14 months and weighing 35–40?kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5?mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group.

RESULTS: Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (p<0.05). The terminal half-life was longer (15.16 (SD 4.74) vs. 10.69 (SD 1.49) hours) and the MRT was shorter (15.67 (SD 2.37) vs. 24.33 (SD 3.12) hours) following S/C than oral administration (p<0.05), but bioavailability was similar (98.24 (SD 9.62) vs. 96.49 (SD 10.71)%).

CONCLUSION AND CLINICAL RELEVANCE: Subcutaneous administration of meloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.     

Plasma profiles of ivermectin in horses following oral or intramuscular administration

A study was undertaken in order to evaluate and compare ivermectin's (IVM) plasma disposition kinetic parameters after oral or intramuscular (IM) administration in horses. Ten clinically healthy adult horses, weighing 380-496 kg body weight (BW), were allocated to two experimental groups of five horses. Group I, was treated with an oral paste formulation of IVM at the manufacturer's recommended dose of 0.2 mg/kg BW. Group II, was treated IM with an injectable 1% formulation of IVM at a dose of 0.2 mg/kg BW. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by high-performance liquid chromatography with fluorescence detection. A computerized kinetic analysis was performed, and data were compared using the Wilcoxon signed rank test. The parent molecule was detected in plasma between 30 min and either 20 (oral) or 40 (IM) days post-treatment. Significant differences were found for the time corresponding to peak plasma concentrations (tmax) and for absorption half-life. Peak plasma concentrations (Cmax) of 51.3 +/- 16.1 ng/ml (mean +/- SD) were obtained after oral administration and of 31.4 +/- 6.0 ng/ml for the IM route. The values for area under concentration-time curve were 137.1 +/- 35.9 ng day/ml for the group treated orally, and 303.2 +/- 4.3 ng day/ml for the IM treated group. The mean plasma residence times were 4.2 +/- 0.4 and 8.9 +/- 0.7 days for oral and IM-treated groups, respectively. The results of this study show that the route of administration considerably affects the disposition of IVM. A significant difference in bioavailabilty and half-life of elimination of IVM was observed after IM administration compared with oral administration. A close relationship between pharmacokinetic profiles and the clinical efficacy of IVM was established.     

Plasma disposition and faecal excretion of eprinomectin following topical and subcutaneous administration in non-lactating dairy cattle

AIMS: To investigate the plasma disposition and faecal excretion of eprinomectin (EPM) in non-lactating dairy cattle following topical and S/C administration.

METHODS: Holstein dairy cows, 3.5–5 years-old, were selected 20–25 days after being dried off and were randomly allocated to receive EPM either topically (n=5) or S/C (n=5) at dose rates of 0.5 and 0.2?mg/kg bodyweight, respectively. Heparinised blood and faecal samples were collected at various times between 1 hour and 30 days after treatment, and were analysed for concentrations of EPM using high performance liquid chromatography with a fluorescence detector.

RESULTS: The maximum concentration of EPM in plasma (C_max) and the time to reach C_max were both greater after S/C administration (59.70 (SD 12.90) ng/mL and 1.30 (SD 0.27) days, respectively) than after topical administration (20.73 (SD 4.04) ng/mL and 4.40 (SD 0.89) days, respectively) (p<0.001). In addition, S/C administration resulted in greater plasma availability (area under the curve; AUC), and a shorter terminal half-life and mean residence time (295.9 (SD 61.47) ng.day/mL; 2.95 (SD 0.74) days and 4.69 (SD 1.01) days, respectively) compared with topical administration (168.2 (SD15.67) ng.day/mL; 4.63 (SD 0.32) days, and 8.23 (SD 0.57) days, respectively) (p<0.01). EPM was detected in faeces between 0.80 (SD 0.45) and 13.6 (SD 4.16) days following S/C administration, and between 1 (SD 0.5) and 20.0 (SD 3.54) days following topical administration. Subcutaneous administration resulted in greater faecal excretion than topical administration, expressed as AUC adjusted for dose (1188.9 (SD 491.64) vs. 311.5 (SD 46.90) ng.day/g; p<0.05). Maximum concentration in faeces was also higher following S/C than topical administration (223.0 (SD 63.96) vs. 99.47 (SD 43.24) ng/g; p<0.01).

CONCLUSIONS: Subcutaneous administration of EPM generated higher plasma concentrations and greater plasma availability compared with topical administration in non-lactating cattle. Although the S/C route provides higher faecal concentrations, the longer faecal persistence of EPM following topical administration may result in more persistent efficacy preventing establishment of incoming nematode larvae in cattle.     

Influence of the type of management system on corticosterone transfer into eggs in laying hens

The effect of free-range versus cage management system on corticosterone transfer into the eggs was studied in laying hens. Hungarian Yellow laying hens (age: 21 weeks, body weight: 2.0 +/- 0.5 kg) were divided into two groups in the spring: Group I, free-range keeping (n=15 layers, density: > 0.5 bird/m2) in outdoor runs, with continuous access to a commercial layer feed; Group II, hens kept in battery cages (n=17 layers, density: 2 birds/m2, natural light, continuous access to feed and water). Eggs were collected after a one-week adaptation period on days 2, 7 and 16. Corticosterone (CST) was extracted from homogenised egg samples using an ASE-200 Accelerated Solvent Extractor and then assayed by liquid chromatography linked with tandem mass spectrometry (LC-MS/MS) [Thermo Quest Surveyor high-performance liquid chromatography (HPLC) interfaced via Atmospheric Pressure Chemical Ionisation (APCI) ion source to Finnigan/Thermo Quest LCQ Deca MS/MS] using dexamethasone as internal standard with positive APCI ionisation. CST concentrations of whole eggs laid by free-range hens on days 2, 7 and 16 were 0.370 +/- 0.218, 0.259 +/- 0.066 and 0.915 +/- 0.745 ng x g(-1), respectively, while those of eggs laid by caged hens were 0.206 +/- 0.157, 0.223 +/- 0.165 and 0.184 +/- 0.110 ng x g(-1) at the above sampling times. It is concluded that in free-range laying hens the sharp changes of environmental weather conditions significantly increased the corticosterone content of eggs, while the environmentally controlled and closed battery cage management technology resulted in relatively uniform corticosterone concentrations in the whole eggs.     

Comparison of the pharmacokinetics of moxidectin (Equest®) and ivermectin (Eqvalan®) in horses

A study was undertaken in order to evaluate and compare plasma disposition kinetic parameters of moxidectin and ivermectin after oral administration of their commercially available preparations in horses. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups of five horses. Group I was treated with an oral gel formulation of moxidectin (MXD) at the manufacturers recommended therapeutic dose of 0.4 mg/kg bw. Group II was treated with an oral paste formulation of ivermectin (IVM) at the manufacturers recommended dose of 0.2 mg/kg b.w. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Computerized kinetic analysis was carried out. The parent molecules were detected in plasma between 30 min and either 30 (IVM) or 75 (MXD) days post-treatment. Both drugs showed similar patterns of absorption and no significant difference was found for the time corresponding to peak plasma concentrations or for absorption half-life. Peak plasma concentrations (Cmax) of 70.3+/-10.7 ng/mL (mean +/- SD) were obtained for MXD and 44.0+/-23.1 ng/mL for IVM. Moreover, the values for area under concentration-time curve (AUC) were 363.6+/-66.0 ng x d/mL for the MXD treated group, and 132.7+/-47.3 ng x d/mL for the IVM treated group. The mean plasma residence times (MRT) were 18.4+/-4.4 and 4.8+/-0.6 days for MXD and IVM treated groups, respectively. The results showed a more prolonged residence of MXD in horses as demonstrated by a four-fold longer MRT than for IVM. The longer residence and the higher concentrations found for MXD in comparison to IVM could possibly explain a more prolonged anthelmintic effect. It is concluded that in horses the commercial preparation of MXD presents a pharmacokinetic profile which differs significantly from that found for a commercial preparation of IVM. To some extent these results likely reflect differences in formulation and doses.     

Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs

This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) following oral and subcutaneous administration (200 microg/kg) over a 40-day period in dogs. Twenty bitches were allocated by weight in to four groups (Groups I-IV) of five animals each. Animals in the first two groups (Groups I and II) received orally the injectable solutions of IVM and DRM, respectively, at the dose of 200 microg/kg bodyweight. The other two groups (Groups III and IV) received subcutaneously injectable solutions at the same dose rate. Blood samples were collected between 1h and 40 days after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that IVM produced a significantly higher maximum plasma concentration (C(max): 116.80+/-10.79 ng/ml) with slower absorption (t(max): 0.23+/-0.09 day) and larger area under the concentration versus time curve (AUC: 236.79+/-41.45 ng day/ml) as compared with DRM (C(max): 86.47+/-19.80 ng/ml, t(max): 0.12+/-0.05 day, AUC: 183.48+/-13.17 ng day/ml) following oral administration of both drugs; whereas no significant differences were observed on the pharmacokinetic parameters between IVM and DRM after subcutaneous administrations. In addition, subcutaneously given IVM and DRM presented a significantly lower maximum plasma concentration (C(max): 66.80+/-9.67 ng/ml and 54.78+/-11.99 ng/ml, respectively) with slower absorption (t(max): 1.40+/-1.00 day and 1.70+/-0.76 day, respectively) and larger area under the concentration versus time curve (AUC: 349.18+/-47.79 ng day/ml and 292.10+/-78.76 ng day/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives ((t(1/2lambda(z)) and mean residence times (MRT) of both molecules. Considering the pharmacokinetic parameters, IVM and DRM could be used by the oral or subcutaneous route for the control of parasitic infection in dogs.     

Pharmacokinetic study of clazuril (Appertex) in eggs and plasma from laying hens after single or multiple treatments, using a new HPLC method for detection

1. Anticoccidials are widely used as food additives to prevent and treat coccidiosis. They are licensed for use in a prescribed concentration and during a specific time interval with broilers and pullets, but not for laying hens. 2. This study was set up to develop a new high pressure liquid chromatography (HPLC) method to detect clazuril (CZ: (+/-)-2-chloro-alpha-(4-chlorophenyl)-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-benzeneacetonitrile) in egg yolk and albumen and in plasma; to investigate both the presence of residues of CZ in eggs and its pharmacokinetic behaviour in laying hens. 3. A single oral dose (3 mg/kg BW) and multiple oral doses (3 mg/kg BW for 5 d) were investigated. The analytical method gave very good recovery (64 to 74%) in the three different matrices (yolk, albumen and plasma); precision and accuracy were within 11%. 4. After a single dose no residue was detected in eggs collected for up to 10 d, while following multiple dose treatment, CZ residues were detected until 10 d after the end of treatment. The concentration of the drug was higher in yolk than in albumen with a maximum ratio of 10 : 1. 5. Pharmacokinetics of CZ in laying hens after a single dose showed a detectable concentration of the drug up to 24 h. It reached a steady state after the third administration in multiple dosing. 6. Although further studies are necessary, these results indicate that a single oral dose of CZ could be used as an anticoccidial for laying hens due to the lack of residues in eggs.     

蛋鸡日粮中添加富硒酵母对鸡蛋中硒含量及分布的影响

试验选用产蛋率约为80%的罗曼褐蛋鸡35只,随机分为7组,进行为期30d的饲养试验。A组为对照组,饲以基础日粮,其余6组为试验组,B、C、D组在基础蛋鸡日粮中分别添加0.2mg/kg、0.5mg/kg、1mg/kg硒的亚硒酸钠,E、F、G组在基础蛋鸡日粮中分别添加0.2mg/kg、0.5mg/kg、1mg/kg硒的富硒酵母。试验过程中记录蛋鸡的生产性能,每隔7d从各试验组鸡所产的鸡蛋中任取3枚,测定鸡蛋中硒的含量,并于试验的第14、15天,28、29天从A、C、F组每组各取5枚鸡蛋分别测定蛋黄和蛋清的硒含量。结果显示,日粮中添加硒对蛋鸡生产性能无显著影响,能极显著提高鸡蛋中硒含量,并且硒主要存在蛋黄中,添加富硒酵母组蛋硒含量较亚硒酸钠组提高更为显著。     

Pharmacokinetics of doramectin and ivermectin after oral administration in horses

A study was undertaken in order to compare plasma disposition kinetic parameters of doramectin (DRM) and ivermectin (IVM) in horses after oral administration. Ten crossbreed adult horses, clinically healthy, weighing 380-470 kg body weight (bw) were selected for study. Faecal examinations were performed to determine faecal parasite egg counts. Horses were allocated to two groups of five animals to provide an even distribution considering the variables sex, body weight and faecal egg count. Group I, were treated with an oral paste formulation of IVM at 0.2 mg/kg b/w and Group II, were treated with an oral dose of 0.2 mg/kg bw of DRM prepared as paste from the injectable formulation for oral administration. Blood samples were collected by jugular puncture between 0 h and 75 days post-treatment. Plasma was separated and later solid phase extraction and derivatization samples were analysed by high performance liquid chromatography (HPLC); a computerised kinetic analysis was carried out. Data were compared using the Mann-Whitney U-test.The mean plasma concentrations of DRM and IVM after oral administration in horses were detected until 30 and 20 days, respectively. Both drugs showed similar patterns of absorption and no significant differences were found for peak concentration, the time to peak concentration, or for absorptive half-life. The terminal elimination half-life was significantly (P<0.05) longer in the DRM treated group than for the IVM treated group. The differences observed in the elimination half-life explain the longer mean residence time and high values of area under the concentration time curve for the group treated with DRM, which are 30% higher than those of the IVM group. Considering its pharmacokinetics, tolerance and anthelmintic efficacy, the oral administration of DRM, could be an alternative to IVM for the control of parasitic diseases of horses.     

Comparison of the coagulation profile of fatty liver haemorrhagic syndrome-susceptible laying hens and normal laying hens

1. The rate of thrombin generation in plasma from Fatty Liver Haemorrhagic Syndrome-susceptible laying hens (FLHS, UCD-003) is more rapid than in plasma from age-matched normal Single Comb White Leghorn (SCWL) laying hens. 2. The rate of thrombin generation in plasma was determined by measuring the biological activity of the specific coagulation proteins, Factors V, VII, VIII, IX and X. 3. The higher activity of Factors V, VII and X in FLHS-susceptible laying hens compared with normal SCWL hens remained consistent after plasma lipid concentrations were reduced. 4. Analysis of the fatty acid composition of plasma phospholipids showed that in normal SCWL laying hens phosphatidylethanolamine contained C18:3n3 whereas it contained C20:3n3 in FLHS-susceptible laying hens. 5. The results suggest that alterations in the composition of the phospholipids that are essential cofactors in the biochemical reactions involved in thrombin generation may be a contributing factor in the development of FLHS.     

Ivermectin disposition kinetics after subcutaneous and intramuscular administration of an oil-based formulation to cattle.

Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p < 0.05) and delayed peak plasma concentration (p < 0.001) were obtained following the SC administration of the IVM-TEST compared to the IVM-CONTROL formulation. No differences in total plasma availability were observed among treatments. However, the plasma residence time and elimination half-life of IVM were significantly longer after injection of the IVM-TEST formulation. IVM plasma concentrations were above 0.5 ng/ml for 20.6 (CONTROL) and 27.5 days (IVM-TEST SC), respectively (p < 0.05). The modified kinetic behaviour of IVM obtained after the administration of the novel oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.     

Characteristics of Salmonella enteritidis contamination in eggs after oral,aerosol, and intravenous inoculation of laying hens

Experimental infection models are useful tools for understanding how Salmonella enteritidis is deposited in eggs and for testing potential strategies to control eggborne transmission of disease to humans. Oral inoculation of laying hens is presumed to provide the closest simulation of naturally occurring infections, but alternatives such as intravenous or aerosol inoculation have sometimes been recommended as options to induce higher incidences of egg contamination. The present study compared the frequency, level, and location of S. enteritidis deposition in egg contents after experimental inoculation by three different routes. In two replicate trials, specific-pathogen-free laying hens were infected with an S. enteritidis culture mixture prepared to optimize invasive behavior. Groups of hens received either an oral dose of 10(9) S. enteritidis, an aerosol dose of 10(9) S. enteritidis, or an intravenous dose of 10(5)-10(7) S. enteritidis. Oral inoculation led to the highest incidence of fecal shedding of S. enteritidis, whereas intravenous inoculation produced the highest specific antibody titers. Eggs laid during the first 21 days postinoculation were cultured to detect and enumerate S. enteritidis in the yolk and albumen. No significant differences were observed among the three inoculation routes in the frequencies of isolation of S. enteritidis from either yolk or albumen. For all three routes of administration, S. enteritidis was recovered more often from yolk (at frequencies ranging from 4% to 7%) than from albumen (0 to 2%). Over 73% of contaminated eggs harbored fewer than 1 colony-forming unit (CFU) of S. enteritidis per milliliter, and only 3% of such eggs contained more than 100 CFUs/ml. Significantly higher levels of S. enteritidis contaminants were associated with intravenous inoculation than with the other routes. No advantage of using aerosol or intravenous administration of S. enteritidis as an alternative to oral inoculation for inducing the production of contaminated eggs was evident in this study.     

Plasma 1,25 dihydroxycholecalciferol and its free index are potentiated by ovulation dependent factors and shell formation induced hypocalcemia in the laying hens.

The time-course of the changes in blood ionized calcium, and in plasma 1,25 dihydroxycholecalciferol (1,25(OH)2D3) concentrations and its free index were studied in hens following suppression and resumption of shell formation and throughout the laying cycle in hens laying hard-shelled eggs, in hens fed a low or normal calcium diet and in hens laying shell-less eggs. The respective roles of the calcium needs for shell formation and of the reproductive status in regulation of 1,25(OH)2D3 production were analysed. Plasma 1,25(OH)2D3 decreased 3 hr after suppression of shell formation following premature egg expulsion and remained lower than that of hens laying hard-shelled eggs when premature expulsion of the eggs was continued for several days. Circulating 1,25(OH)2D3 tended to increase progressively when shell formation was resumed. Ablation of the parathyroid glands abolished this increase. In hens laying hard-shelled eggs, the plasma 1,25(OH)2D3 was higher during the period of shell secretion. Feeding hens a low calcium diet (1.2%) caused a marked increase in the plasma 1,25(OH)2D3. Ionized calcium levels tended to show reciprocal changes to plasma 1,25(OH)2D3 decreasing when calcification took place and increasing after its suppression. In hypercalcemic hens laying shell-less eggs and fed a 3.5% Ca diet, the plasma 1,25(OH)2D3 was at a high level 4 hr after ovulation and diminished thereafter. This additive stimulation does not, therefore, involve the parathyroid gland and may involve hormonal changes induced by ovulation. Vitamin D binding protein (DBP) in the plasma was at a high level in mature hens and was not affected by shell formation. Consequently, the free 1,25(OH)2D3 index fluctuated in parallel with total level of this hormone in mature hens. It is concluded that the calcium demand for shell formation modulates, in the short term, plasma 1,25(OH)2D3, via the homeostatic regulation of blood calcium by PTH, but that a large part of its increase is independent of PTH and is associated with the endocrine events concomitant with ovulation.     

Albendazole treatment in laying hens: Egg residues and its effects on fertility and hatchability

This work characterized the egg residual concentrations of albendazole (ABZ ) and its sulphoxide (ABZSO ) and sulphone (ABZSO ₂) metabolites and evaluated their effect on egg fertility and hatchability after ABZ treatments to laying hens. Seventy hens were allocated in groups: Group‐1 was the control without treatment; Group‐2 received a single ABZ oral dose (10 mg/kg); Group‐3, ‐4 and ‐5 were treated with ABZ in medicated feed over 7 days at 10, 40, or 80 mg kg^?1 day^?1, respectively. Eggs were analyzed to determine the ABZ /metabolite level by HPLC or subjected to incubation to evaluate the fertility and hatchability. Only ABZSO and ABZSO ₂ metabolites were quantified in egg after ABZ single oral administration with maximum concentrations of 0.47 ± 0.08 and 0.30 ± 0.07 μg/ml, respectively. ABZ and its metabolites were found in eggs after 7‐day ABZ treatments. The egg residue exposure estimated as AUC s (areas under the concentration vs . time curve) were 100.5 (ABZ ), 56.3 (ABZSO ) and 141.3 μg hr g^?1 (ABZSO ₂). ABZ administration did not affect the egg fertility at any dosages. Egg hatchability was not affected by ABZ treatment at 10 mg/kg in medicated feed, but it decreased when the dose was 4–8 times higher. These results should be considered when ABZ is used for deworming laying hens.     

Disposition of metronidazole in hens (Gallus gallus) and quails (Coturnix coturnix japonica): pharmacokinetics and whole-body autoradiography

Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half-life ( t _1/2β) after the intravenous injection was 4.2 ± 0.5 h, the volume of distribution ( V _d(ss)) 1.1±0.2 L/kg and the total body clearance ( Cl _B) 131.2 ± 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 ± 16%. The plasma maximum concentration ( C _max) 31.9 ± 2.3 μg/mL was reached 2 h after the oral administration and the oral elimination half-life ( t ₁/2β) was 4.7 ± 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [³H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1-4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/kg metronidazole.     

Plasma disposition and renal clearance of sulphadimidine and its metabolites in laying hens

Plasma disposition of sulphadimidine (SDM) and its metabolites was studied in laying hens after 100 mg SDM kg-1 doses were administered as a single intravenous dose, a single oral dose and multiple oral doses once daily for five consecutive days. SDM was extensively metabolised by acetylation and hydroxylation. In plasma, the metabolite observed with the highest concentration was N4-acetylsulphadimidine (N4-SDM) followed by hydroxymethylsulphadimidine (CH2OH) and 5-hydroxysulphadimidine. Following intravenous administration a biphasic elimination (as seen for a capacity limited reaction) pattern for SDM and its metabolites was observed. Multiple (5x) SDM dosing revealed plasma SDM concentrations ranging between 7 and 108 micrograms ml-1; within 96 hours of termination of the multiple SDM dosing, the plasma SDM concentration was below 0.01 micrograms ml-1. The renal clearances of N4-SDM and the hydroxy metabolites were approximately 10 times greater than that of SDM. The SDM mass balance (faecal/urinary recovery) showed a loss of 56 per cent after intravenous dosage and of 67 per cent after a single oral dosage; the hydroxy metabolites accounted for the highest percentage in faeces/urine. Thus additional metabolic pathways must exist in laying hens.     

植物乳酸杆菌对感染沙门氏菌蛋鸡血浆生化、免疫水平及沙门氏菌定植的影响

本试验旨在研究植物乳酸杆菌对感染肠炎沙门氏菌蛋鸡血浆生化、免疫水平及沙门氏菌定植的影响。将400只京红1号商品代蛋鸡随机分成4个处理组,每组5个重复,每个重复20只鸡。A组和C组饲喂基础饲粮,B组和D组在基础饲粮添加2×10~8 CFU/g植物乳酸杆菌。饲喂1周后,C组和D组连续2 d口服1×10~10CFU/m L肠炎沙门氏菌菌液,A组和B组口服等量无菌PBS溶液,饲养3周。结果表明:添加植物乳酸杆菌可显著提升总蛋白、球蛋白水平(P0.05),显著降低低密度脂蛋白和甘油三酯(P0.05);添加植物乳酸杆菌可显著增加IgM、IgG(P0.05);蛋鸡感染沙门氏菌的第14天和第21天及试验全程,添加植物乳酸杆菌显著减少盲肠食糜中肠炎沙门氏菌拷贝数(P0.05)。综上可知,日粮中添加植物乳酸杆菌可改善感染肠炎沙门氏菌蛋鸡的血浆生化指标,缓解炎症损伤,降低盲肠沙门氏菌定植数量,保障机体健康。     

Plasma prolactin concentrations in broody turkeys: Lack of agreement between homologous chicken and turkey prolactin radioimmunoassays

1. Plasma concentrations of prolactin, measured using homologous chicken or turkey prolactin radioimmunoassays, increased 2‐ and 9‐fold, respectively in somatically mature turkey hens transferred from short (6 h light (L) :18 h dark (D)) to long (14 L:10 D) photoperiods.

2. A further increase in plasma prolactin was observed in laying hens 2 to 3 weeks before the onset of incubation. This increase was detected using the turkey prolactin assay but not the chicken prolactin assay.

3. The onset of incubation was not always associated with the cessation of egg production. Egg laying stopped in incubating hens only after plasma concentrations of prolactin were approaching their maximal values. These were 10‐fold higher than the prolactin concentrations at the onset of lay.

4. The removal of clutches of eggs from incubating hens resulted in a decrease in plasma concentrations of prolactin, which was associated with the cessation of incubation in two hens which had been incubating for 52 and 47 d. The decrease was only temporary in two hens which had been incubating for 8 and 32 d. The latter two hens continued to show incubation behaviour although they were not sitting on eggs.

5. In four turkey hens which did not become broody, egg production ceased after 12 weeks exposure to 14 L: 10 D. The concentration of plasma prolactin, as measured using the turkey prolactin assay, increased 2‐fold during the 2 weeks before these hens stopped laying.     

The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour-on administration in goats

Gokbulut, C., Cirak, V.Y., Senlik, B., Aksit, D., McKellar, Q.A. The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour‐on administration in goats. J. vet. Pharmacol. Therap. 34 , 70–75. The effects of different ages and dosages on the plasma disposition and hair degradation of ivermectin (IVM) were investigated following pour‐on administration in goats. Twenty‐eight female Saanen goats allocated into two groups of 14 animals according to their ages as young (5–6 months old) and old (12–24 months old) groups. Each age group was divided into two further of seven goats and administered pour‐on formulation of IVM topically at the in recommended dosage rate of 0.5 mg/kg bodyweight The recommended cattle dosages rate of 0.5 mg/kg or at the higher dosage of 1.0 mg/kg. Blood samples were collected at various times between 1 h and 40 days. In addition, hair samples (>0.01 g) were collected using tweezers from the application sites and far from application sites of the all animals throughout the blood sampling period. The plasma and hair samples were analyzed by high performance liquid chromatography (HPLC) using fluorescence detection following solid and liquid phase extractions, respectively. Dose‐ and age‐dependent plasma disposition of IVM were observed in goats after pour‐on administration. In addition, relatively high concentration and slow degradation of IVM in hair samples collected from the application site and far from the application site were observed in the present study. The differences between young and old goats are probably related to differences in body condition and/or lengths of haircoat. The systemic availability of IVM following pour‐on administration is relatively much lower than after oral and subcutaneous administrations but the plasma persistence was prolonged. Although, the longer persistence of IVM on hairs on the application site may prolong of efficacy against ectoparasites, the poor plasma availability could result in subtherapeutic plasma concentrations, which may confer the risk of resistance development in for internal parasites after pour‐on administration in goats.