Population pharmacokinetics for danofloxacin in the intestinal contents of healthy and infected chickens

Avian pathogenic Escherichia coli could cause localized and systemic infection in the poultry, and danofloxacin is usually used to treat avian colibacillosis through oral administration. To promote prudent use of danofloxacin and reduce the emergence of drug‐resistant E. coli strains, it is necessary to understand the population pharmacokinetics (PopPK) of danofloxacin in chicken intestines. In this study, reversed‐phase high performance liquid chromatography (HPLC) with fluorescence detection was used to detect the concentrations of danofloxacin in the contents of duodenum, jejunum, and ileum of the healthy and infected chickens after single oral administration (5 mg/kg body weight). Then, the PopPK of danofloxacin in intestines were analyzed using NONMEM software. As a result, a two‐compartment PK model best described the time‐concentration profile of duodenal, jejunal, and ileal contents. Interestingly, absorption rate (K_a), distribution volume (V), and clearance (CL) for danofloxacin from duodenal, jejunal to ileal contents were sequentially decreased in the healthy chickens. However, the trend of K_a, V, and CL of danofloxacin was changed dramatically in the intestine of infected chickens. K_a and V of danofloxacin in the jejunum were higher than in the ileum and duodenum. Compared with healthy chickens, K_a and V of danofloxacin in the duodenum decreased significantly, while increased in jejunum, respectively. It has been noted that K_a decreased and V increased in the ileum of infected chickens. Besides, CL in the duodenum, jejunum, and ileum of infected chickens was, respectively, lower than those of healthy chickens. Interestingly, the relative bioavailability (F) of danofloxacin in the ileum was relatively higher in both healthy and infected chickens. In addition, F in the duodenal, jejunal, and ileal contents of infected chickens was respectively higher than healthy chickens. In summary, the PopPK for danofloxacin in infected chicken intestines was quite different from healthy chickens. The absorption, distribution, and clearance of danofloxacin in healthy chickens decreased from duodenum to jejunum and to ileum. Moreover, the pharmacokinetic characteristics in the intestine of infected chickens changed significantly, and the pharmacokinetic characteristics in the ileum can be used as a representative of all intestinal segments.     

单诺沙星在健康与支原体-大肠杆菌合并感染鸡体内的药动学研究

以高压液相色谱 (HPLC)法为定量手段研究了单诺沙星在健康和支原体与大肠杆菌合并感染鸡体内的药动学特征。 60只健康鸡和 60只合并感染鸡内服单诺沙星 (5mg/kg)后 ,血浆的药时数据均符合一级吸收二室模型。健康和合并感染鸡的主要动力学参数分别如下 :t1 /2ka为 0 2 4 2 8和 0 31 82h,t1 /2α为 0 891 7和 1 550 2h ,t1 /2 β为 8 793 6和 1 2 62 0 0h ,Tp为 0 9377和 1 1 1 0 7h ,Cmax为 0 5487和 0 51 0 6μg/mL ,每小时为3 0 52 3和 3 660 2mg/L ,Tcp为 31 1 1 5和 39 1 8h。单诺沙星在鸡体内的药动学特征是吸收迅速且完全 ,体内分布广泛 ,但消除缓慢 ,有效浓度维持时间长。合并感染使单诺沙星在感染鸡体内的吸收、分布和消除均减慢 ,达峰时间、有效浓度维持时间延长     

Comparison of the pharmacokinetics of tilmicosin in plasma and lung tissue in healthy chickens and chickens experimentally infected with Mycoplasma gallisepticum

The objectives of this study were to compare the plasma and lung tissue pharmacokinetics of tilmicosin in healthy and Mycoplasma gallisepticum-infected chickens. Tilmicosin was orally administered at 4, 7.5 and 10 mg/kg body weight (b.w) for the infected and 7.5 mg/kg b.w for the uninfected control group. We found no significant differences in plasma tilmicosin pharmacokinetics between diseased and healthy control chickens. In contrast, the lung tissues in M. gallisepticum-infected chickens displayed a t_1/2 (elimination half-life) 1.76 times longer than for healthy chickens. The C_max (the maximum concentration of drug in samples) of tilmicosin in M. gallisepticum-infected chickens was lower than for controls at 7.5 mg/kg b.w (p < .05), and the AUC_inf (the area under the concentration–time curve from time 0 extrapolated to infinity) in infected chickens was higher than for the healthy chickens (p < .05). The mean residence time of tilmicosin in infected chickens was also higher than the healthy chickens. These results indicated that the lungs of healthy chickens had greater absorption of tilmicosin than the infected chickens, and the rate of elimination of tilmicosin from infected lungs was slower.     

Mycoplasma gallisepticum and Escherichia coli mixed infection model in broiler chickens for studying valnemulin pharmacokinetics

A Mycoplasma gallisepticum–Escherichia coli mixed infection model was developed in broiler chickens, which was applied to pharmacokinetics of valnemulin in the present experiment. The velogenic M. gallisepticum standard strain S6 was rejuvenated to establish the animal model, and the wild E. coli strain O78 was injected as supplementary inoculum to induce chronic respiratory disease in chickens. The disease model was evaluated based on its clinical signs, histopathological examination, bacteriological assay, and serum plate agglutination test. The pharmacokinetics of valnemulin in infected chickens was determined by intramuscular (i.m.) injection and oral administration (per os, p.o.) of a single dose of 10 mg/kg body weight (BW). Plasma samples were analyzed by liquid chromatography–tandem mass spectrometry. The plasma concentration–time curve of valnemulin was analyzed using the noncompartmental method. After the i.m. administration, the mean values of C_max, T_max, AUC_last, MRT, CL_β/F, V_z/F, and t_1⁄2β, were 27.94 μg/mL, 1.57 h, 171.63 μg·h/mL, 4.51 h, 0.06 L/h/kg, 0.56 L/kg, and 6.50 h, respectively. By contrast, the corresponding values after p.o. administration were 5.93 μg/mL, 7.14 h, 47.60 μg·h/mL, 9.80 h, 0.22 L/h/kg, 3.35 L/kg, and 10.60 h. The disposition of valnemulin was retarded in infected chickens after both modes of extravascular administration as compared to the healthy controls. More attention should be given to monitoring the therapeutic efficacy and adverse effects of mixed infection because of higher required plasma drug concentration and enlarged AUC with valnemulin treatment.     

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

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

Pharmacokinetics and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous,intramuscular, subcutaneous,and oral administrations

The aim of the present study was to determine the pharmacokinetics (PKs) and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg. A total of eight clinically healthy chukar partridges weighing 480 ± 45 g were used for the investigation. The study was performed in a crossover design (2 × 2 × 2 × 2) with a 15‐day washout period between two administrations in four periods. The plasma concentrations of danofloxacin were determined using reversed‐phase high‐performance liquid chromatography. Noncompartmental PK parameters were also estimated. No local or systemic adverse drug effects were observed in any of the chukar partridges. The mean elimination half‐life ranged between 8.18 and 12.08 hr and differed statistically among administration routes. The mean peak plasma concentrations of danofloxacin following IM, SC, and PO administrations were 8.05, 9.58, and 3.39 μg/ml at 0.5, 1, and 4 hr, respectively. Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean total clearance and volume of distribution at steady‐state following IV administration were 0.13 L hr^?1 kg^?1 and 0.96 L/kg, respectively. These data, including favorable PKs and the absence of adverse drug effects, suggest that danofloxacin is a useful antibiotic in chukar partridges.     

Development of a multiroute physiologically based pharmacokinetic model for orbifloxacin in rabbits

To predict the orbifloxacin concentrations in rabbits after multiple routes of administration, a flow‐limited multiroute physiologically based pharmacokinetic (PBPK) model was developed. Three routes of administration (IV, IM, and PO) were incorporated into this model. Physiological parameters including tissue weights and blood flows through different tissues were obtained from the literature. The tissue/plasma partition coefficients (P_Xs) for noneliminating tissues were calculated according to the area method, while the P_Xs for kidney and the rest of the body compartment, together with other parameters for absorption and elimination, were optimized based on the published concentrations. The comparisons between predicted and observed orbifloxacin concentrations proved its validity, and the present model predicted available concentration data well, including those in liver, kidney, muscle, lung, heart, and plasma after oral, intravenous, or intramuscular administration. A local sensitivity analysis was also performed, which showed that the parameters for oral absorption were most influential on the orbifloxacin concentrations. This model was used to predict plasma and tissue concentrations after multiple oral or intramuscular administration. This study demonstrated the feasibility of predicting drug residues in minor species after multiple routes of administration in the extra‐label manner using the PBPK modeling.     

Anticoccidial activity of the methanolic extract of Musa paradisiaca root in chickens

The study was designed to evaluate the anticoccidial activity of the methanolic extract of Musa paradisiaca root in chickens. The chickens were divided into six groups of 12 chickens each. Each chicken in five groups was infected with 8,000 infective coccidia (Eimeria tenella) oocysts at day 28 of age while one group served as uninfected control. At day 7 post-infection, two chickens remaining in each group were sacrificed for postmortem examination to confirm coccidiosis. Also at day 7 post-infection, each chicken in four infected groups was given graded doses (250, 500 and 1,000 mg/kg b.w.) of the extract or amprolium (conventional drug). Two groups (an infected and uninfected group) did not receive treatment. Parameters used to assess progress of infection and response to treatment included clinical signs typical of coccidiosis, oocyst count per gramme of faeces (OPG) and packed cell volume (PCV). Treatment of previously infected chickens with M. paradisiaca root extract resulted in a progressive decrease in severity of observed clinical signs, marked reductions in OPG and a gradual increase in PCV. In each case, the changes were dose dependent. There was no significant difference in mean OPG and mean PCV of the extract (at 1,000 mg/kg b.w.) and amprolium-treated groups at termination of the study (at day 50 of age). In the acute toxicity study, the extract was found to be non-toxic to the chickens even at the highest dose of 4,000 mg/kg b.w. The results of this study demonstrated that the extract has anticoccidial activity in a dose-dependent manner and at a dosage of 1,000 mg/kg b.w. had similar efficacy with amprolium in the treatment of chicken coccidiosis.     

Pharmacokinetics,urinary excretion and plasma protein binding of danofloxacin following intravenous administration in buffalo calves (Bubalus bubalis)

Pharmacokinetics, urinary excretion and plasma protein binding of danofloxacin was investigated in buffalo calves following intravenous administration at the dose rate of 1.25 mg/kg to select the optimal dosage regimen of danofloxacin. Drug concentrations in plasma and urine were measured by microbiological assaying. In vitro plasma protein binding was determined employing the equilibrium dialysis technique. The distribution and elimination of danofloxacin were rapid, as indicated by values (mean ±SD) of distribution half-life (t_1/2α = 0.16 ± 0.07 h) and elimination half-life (t_1/2β = 4.24 ± 1.78 h), respectively. Volume of distribution at steady state (Vss) = 3.98 ± 1.69 L/kg indicated large distribution of drug. The area under plasma drug concentration versus time curve (AUC) was 1.79 ± 0.28 μg/mlxh and MRT was 8.64 ± 0.61 h. Urinary excretion of danofloxacin was 23% within 48 h of its administration. Mean plasma protein binding was 36% at concentrations ranging from 0.0125 μg/ml to 1 μg/ml. On the basis of pharmacokinetic parameters obtained, it is concluded that the revision of danofloxacin dosage regimen in buffalo calves is needed because the current dosage schedule (1.25 mg/kg) is likely to promote resistance.     

Comparative study of the plasma pharmacokinetics and tissue concentrations of danofloxacin and enrofloxacin in broiler chickens

The plasma pharmacokinetics of danofloxacin and enrofloxacin in broiler chickens was investigated following single intravenous (i.v.) or oral administration (p.o.) and the steady-state plasma and tissue concentrations of both drugs were investigated after continuous administration via the drinking water. The following dosages approved for the treatment of chickens were used: danofloxacin 5 mg/kg and enrofloxacin 10 mg/kg of body weight. Concentrations of danofloxacin and enrofloxacin including its metabolite ciprofloxacin were determined in plasma and eight tissues by specific and sensitive high performance liquid chromatography methods. Pharmacokinetic parameter values for both application routes calculated by noncompartmental methods were similar for danofloxacin compared to enrofloxacin with respect to elimination half-life (t1/2: approximately 6-7 h), mean residence time (MRT; 6-9 h) and mean absorption time (MAT; 1.44 vs. 1.20 h). However, values were twofold higher for body clearance (ClB; 24 vs. 10 mL/min. kg) and volume of distribution at steady state (VdSS; 10 vs. 4 L/kg). Maximum plasma concentration (Cmax) after oral administration was 0.5 and 1.9 micrograms/mL for danofloxacin and enrofloxacin, respectively, occurring at 1.5 h for both drugs. Bioavailability (F) was high: 99% for danofloxacin and 89% for enrofloxacin. Steady-state plasma concentrations (mean +/- SD) following administration via the drinking water were fourfold higher for enrofloxacin (0.52 +/- 0.16 microgram/mL) compared to danofloxacin (0.12 +/- 0.01 microgram/mL). The steady-state AUC0-24 h values of 12.48 and 2.88 micrograms.h/mL, respectively, derived from these plasma concentrations are comparable with corresponding area under the plasma concentration-time curve (AUC) values after single oral administration. For both drugs, tissue concentrations markedly exceeded plasma concentrations, e.g. in the target lung, tissue concentrations of 0.31 +/- 0.07 microgram/g for danofloxacin and 0.88 +/- 0.24 microgram/g for enrofloxacin were detected. Taking into account the similar in vitro activity of danofloxacin and enrofloxacin against important pathogens in chickens, a higher therapeutic efficacy of water medication for enrofloxacin compared to danofloxacin can be expected when given at the approved dosages.     

达氟沙星脂质体在蛋雏鸡体内的组织动力学及靶向性研究

将260只28日龄试验鸡(体质量215~230 g)随机分成5组:健康对照组20只,甲磺酸达氟沙星溶液静注给药组和内服给药组、甲磺酸达氟沙星脂质体静注给药组和内服给药组,每组60只。以5 mg/kg体质量剂量分别采用静脉注射和内服2种给药途径给予健康蛋雏鸡甲磺酸达氟沙星溶液和脂质体混悬液,于给药后0.167、0.333、0.5、0.75、1、1.5、2、4、6、9、12、24 h各剖杀5只鸡,取血液、肝脏、肾脏、肺脏和肌肉样品。采用反相HPLC色谱内标法测定各组织中达氟沙星浓度。应用MCPKP分析软件处理血浆药物浓度-时间数据,比较2种剂型的组织药动学参数。结果显示,与溶液组相比,甲磺酸达氟沙星脂质体组肝脏、肺脏中的药物分布明显提高,肾脏中的分布降低;通过相对摄取率、靶向效率和峰浓度比3个靶向指标的对比,脂质体组明显提高了肺部靶向性,且在肺部有一定的缓释作用。     

Genome-wide association study of body size traits in Wenshang Barred chickens based on the specific-locus amplified fragment sequencing technology

Chicken body size (BS) is an economically important trait, which has been assessed in many studies for genetic selection. However, previous reports detected functional chromosome mutations or regions using gene chips. The present study used the specific-locus amplified fragment sequencing (SLAF-seq) technology to perform a genome-wide association study (GWAS) of purebred Wenshang Barred chickens. A total of 250 one-day-old male chickens were assessed in this study. Body size in individual birds was measured at 56 days. SLAF-seq was used to genotype and GWAS analysis was carried out using the general linear model (GLM) of the TASSEL program. A total of 1,286,715 single-nucleotide polymorphisms (SNPs) were detected, of which 175,211 were tested as candidate SNPs for genome-wide association analysis using the TASSEL general linear model. Three SNPs markers reached genome-wide significance. Of these, chrZ:81729634, chrZ:81841715, and chrZ:81954149 at 81,729,634, 81,841,715, and 81,954,149 bp of GGA Z were significantly associated with body diagonal length at 56 days (BDL56); and tibia length at 56 days (TL56). These SNPs were close to three genes, including ZCCHC7, PAX5, and MELK. These results open new horizons for studies on BS and should promote the use of Chinese chickens, especially Wenshang Barred chickens.     

Inclusion of Bacillus amyloliquefaciens strain TOA5001 in the diet of broilers suppresses the symptoms of coccidiosis by modulating intestinal microbiota

Coccidiosis is an intestinal parasitic infection and one of the most prevalent and economically damaging diseases of chickens. Furthermore, coccidia‐induced mucogenesis promotes secondary colonization by Clostridium perfringens, a major pathogen of chickens that causes necrotic enteritis. Our previous work found that supernatant of a culture of Bacillus amyloliquefaciens strain TOA5001 (BA) inhibited the growth of C. perfringens on Gifu anaerobic broth medium. Accordingly, we evaluated the effectiveness of dietary BA administration in inhibiting C. perfringens colonization of the intestine in broilers that were experimentally infected with coccidia. Ten healthy broilers from a BA‐supplemented (2 × 10⁵ colony‐forming units/g of feed) broiler group and 10 from a non‐treated group were challenged with Eimeria tenella and E. maxima (5000 oocysts of each species/chick) at 28 days old. At 36 days old, five chicks from each group were slaughtered, whereas the remaining five in each group were killed at 49 days old. Dietary BA administration into Eimeria‐challenged birds reduced coccidial symptoms such as intestinal lesions. It also modified the cecal microbiota through suppressing C. perfringens and E. coli colonization, and inducing domination of Faecalibacterium prausnitzii, the Lactobacillus group and unknown Lachnospiraceae genera by bacterial DNA‐based metagenome analyses. B. amyloliquefaciens TOA5001 supplementation suppressed the symptoms of coccidiosis by modulating cecal microbiota in Eimeria‐challenged broilers.     

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.     

Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin phosphate after a single oral and i.v. administration in chickens

The pharmacokinetics and oral bioavailability of tylosin tartrate and tylosin phosphate were carried out in broiler chickens according to a principle of single dose, random, parallel design. The two formulations of tylosin were given orally and intravenously at a dose level of 10 mg/kg b.w to chicken after an overnight fasting (n = 10 chickens/group). Serial blood samples were collected at different time points up to 24 h postdrug administration. A high performance liquid chromatography method was used for the determination of tylosin concentrations in chicken plasma. The tylosin plasma concentration's time plot of each chicken was analyzed by the 3P97 software. The pharmacokinetics of tylosin was best described by a one‐compartmental open model 1st absorption after oral administration. After intravenous administration the pharmacokinetics of tylosin was best described by a two‐compartmental open model, and there were no significant differences between tylosin tartrate and tylosin phosphate. After oral administration, there were significant differences in the C_max (0.18 ± 0.01, 0.44 ± 0.09) and AUC (0.82 ± 0.05, 1.57 ± 0.25)between tylosin phosphate and tylosin tartrate. The calculated oral bioavailability (F) of tylosin tartrate and tylosin phosphate were 25.78% and 13.73%, respectively. Above all, we can reasonably conclude that, the absorption of tylosin tartrate is better than tylosin phosphate after oral administration.     

The effects of the supplementation of multi‐strain probiotics on intestinal microbiota,metabolites and inflammation of young SPF chickens challenged with Salmonella enterica subsp. enterica

This study assessed the effect of probiotics on cecal microbiota, cecal short‐chain fatty acids (SCFAs), and the gene expression of cytokines in young specific‐pathogen‐free (SPF) chickens infected with S. enterica subsp. enterica. One‐day‐old SPF chickens (n = 105) were randomly assigned to one of the three treatment groups: control (Cont) group, Salmonella‐infected (Sal) group, and a Salmonella‐infected group treated with multi‐strain probiotics (ProSal group). All chickens except those in the Cont group were challenged orally with 1 × 10⁸ cfu/ml of Salmonella 4 days after hatching. Chickens in the Sal group exhibited more abundance of Proteobacteria than those in the Cont and ProSal groups. At the genus level, chickens in ProSal group exhibited increased numbers of Lactobacillus and Oscillospira compared with those in the other groups. Chickens in the ProSal group exhibited a significant increase of cecal SCFAs compared with chickens in the Sal group. Chickens in the ProSal group exhibited increased gene expression of anti‐inflammatory cytokines, IL‐10 and TGF‐β4, and decreased expression of the proinflammatory cytokine, IFN‐γ, in the cecal tonsil compared with those in the Sal group. The results of this study indicated that the administration of probiotics can modulate microbiota, SCFAs, and immunomodulatory activity in SPF chickens.     

Comparative pharmacokinetics of enrofloxacin in healthy and Aeromonas hydrophila‐infected crucian carp (Carassius auratus gibelio)

The comparative pharmacokinetics of enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP) were investigated in healthy and Aeromonas hydrophila‐infected crucian carp after a single oral (p.o.) administration at a dose of 10 mg/kg at 25 °C. The plasma concentrations of ENR and of CIP were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR concentrations by noncompartmental modeling. In healthy fish, the elimination half‐life (T_1/2λz), maximum plasma concentration (C_max), time to peak (T_max), and area under the concentration–time curve (AUC) values were 64.66 h, 3.55 μg/mL, 0.5 h, and 163.04 μg·h/mL, respectively. In infected carp, by contrast, the corresponding values were 73.70 h, 2.66 μg/mL, 0.75 h, and 137.43 μg·h/mL, and the absorption and elimination of ENR were slower following oral administration. Very low levels of CIP were detected, which indicates a low extent of deethylation of ENR in crucian carp.     

A physiologically based pharmacokinetics model for florfenicol in crucian carp and oral‐to‐intramuscular extrapolation

Yang, F., Sun, N., Sun, Y. X., Shan, Q., Zhao, H. Y., Zeng, D. P., Zeng, Z. L. A physiologically based pharmacokinetics model for florfenicol in crucian carp and oral‐to‐intramuscular extrapolation. J. vet. Pharmacol. Therap.  36 , 192–200. In this study, an oral physiologically based pharmacokinetics (PBPK) model was developed for florfenicol in crucian carp (Carassius auratus). Subsequently, oral‐to‐intramuscular extrapolation was performed and the two models were used to predict florfenicol concentrations in the edible tissues of crucian carp. The oral model gave good predictions in most tissues, except for kidney and liver in which the florfenicol concentrations were underestimated at the later time points. In contrast, using the intramuscular model, the concentrations in the kidney were overestimated at the later time points. Both models had the best predictive ability in the main edible tissue, the muscle. The oral model also accurately predicted the florfenicol concentrations in the muscle after multiple doses. The present study demonstrated the feasibility of predicting florfenicol concentrations in the edible tissues of crucian carp using a route‐to‐route extrapolation method.     

Pharmacokinetic depletion phase of doxycycline in healthy and Mycoplasma gallisepticum‐infected chicken broilers after coadministration of enrofloxacin traces

The objective of this study was to investigate the influence of enrofloxacin (ENR) traces on doxycycline (DC) pharmacokinetic depletion phase parameters in plasma and lungs of healthy and Mycoplasma gallisepticum (MG)‐infected chicken broilers. The multiple‐dose oral administration of DC to chickens which were permanently exposed on ENR traces significantly increased concentration of DC in plasma and lung. It also prolonged the DC elimination time in both healthy and infected animals after final dose. The obtained result indicated that simultaneous administration of DC and ENR in chicken broilers therapy should be avoided.     

Disposition kinetics of danofloxacin and ciprofloxacin in broiler chickens.

Disposition kinetics of danofloxacin and ciprofloxacin were studied in broiler chickens following intravenous, intramuscular and oral administration in a single dose of 5 and 10 mg/kg-1 body weight respectively. In addition, tissue distribution and residual pattern of both drugs were determined. The maximum serum concentration (Cmax) after intramuscular and oral administration were 1.03 and 0.55 mu/ml for danofloxacin and 2.92 and 1.24 mu/ml for ciprofloxacin attained at 0.8 and 2.43 and 0.55 and 1.27 hours for danofloxacin and ciprofloxacin respectively. The volume of distribution and systemic bioavailability were higher for danofloxacin (Vdss 2.21 L/kg and F% 96.56 and 81.4%) as compared with ciprofloxacin (Vdss 1.41 L/kg and F% 75.5 and 29.4%). Data relating to intravenous injection for both drugs were analyzed using a two compartment open model curve fit. Danofloxacin and ciprofloxacin were not detected in the serum of broilers at the 5th and 3rd day respectively following the drugs withdrawal while were detected in liver, kidneys, spleen and lungs. Danofloxacin completely disappeared from all tissues at the 13th day after stopping of the drug medication but ciprofloxacin disappeared after 5 days only.