Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves

The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.     

Pharmacokinetics and tissue distribution of amoxicillin in healthy and Salmonella Typhimurium-inoculated pigs

OBJECTIVE: To determine pharmacokinetics and tissue distribution of amoxicillin in healthy and Salmonella Typhimurium-inoculated pigs. ANIMALS: 12 healthy pigs and 12 S Typhimurium-inoculated pigs. PROCEDURE: Concentration of amoxicillin in tissue was measured by use of high-performance liquid chromatography 4, 8, 12, and 24 hours after IM administration. Pharmacokinetic values of amoxicillin in plasma were assessed by use of a 1-compartment model with first-order absorption. RESULTS: Inoculation caused diarrhea and increased rectal temperature and WBC count. Absorption half-life was shorter in inoculated pigs (0.26 hours) than in healthy pigs (0.71 hours), and inoculated pigs had longer elimination half-life. Distribution ratios in healthy pigs ranged from 0.31 to 0.56 and in inoculated pigs ranged from 0.14 to 0.48. Ratios for distribution to intestinal mucosa ranged from 0.34 to 1.16 in healthy pigs and from 0.22 to 0.36 in inoculated pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Salmonella Typhimurium inoculation altered absorption of amoxicillin from the injection site and prolonged elimination half-life. However, distribution of amoxicillin to intestinal tract tissue was only affected to a minor degree.     

Influence of a pig respiratory disease on the pharmacokinetic behaviour of amoxicillin after oral ad libitum administration in medicated feed

The pharmacokinetic properties of amoxicillin in healthy and respiratory-diseased pigs were studied, after ad libitum administration of medicated feed. In addition, amoxicillin dose linearity and drug penetration into respiratory tract tissues were evaluated in diseased animals. The respiratory disease involves porcine reproductive and respiratory syndrome virus and bacterial agents such as Pasteurella multocida, Bordetella bronchiseptica and Streptococcus suis. Typical clinical signs and gross lesions of respiratory disease were observed. The plasma pharmacokinetic analysis was performed by means of a noncompartmental approach. After single intravenous bolus administration of amoxicillin to healthy pigs, the steady-state volume of distribution was 0.61 L/kg, the total plasma clearance was 0.83 L/h/kg and the mean residence time was 0.81 h. After oral bolus administration, the mean absorption time was 1.6 h and the peak plasma concentration (3.09 μg/mL) reached at 1.1 h postadministration. The oral bioavailability was 34%. For oral ad libitum administration, plasma concentration-time profiles were related to the feeding behaviour. Plasma concentrations at steady-state were established between 12 and 120 h. The pharmacokinetic parameters calculated (C(maxss) , C(minss) , C(avss) and AUC(24ss) ) showed significantly lower values in healthy pigs compared to diseased animals. This was in accordance with the significantly higher amoxicillin bioavailability (44.7% vs. 14.1%) and longer absorption period observed in diseased pigs. Amoxicillin dose linearity in diseased animals was established in a dose range of 4-18 mg/kg. On the other hand, tissue distribution ratio in diseased animals was 0.65 for bronchial mucosa, 0.48 for lung tissue and 0.38 for lymph nodes. Our results suggest that the pharmacokinetic properties and disposition of amoxicillin can be influenced by the disease state or by related factors such as changes in the gastrointestinal transit.     

Influence of Escherichia coli endotoxin-induced fever on the pharmacokinetic behavior of marbofloxacin after intravenous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in seven healthy goats and in the same goats with induced fever after single-dose intravenous (i.v.) administration of 2 mg/kg b.w. Fever was induced by the administration of Escherichia coli endotoxin. Drug concentration in plasma was determined by high-performance liquid chromatography (HPLC). Drug distribution was somehow altered by fever as febrile goats showed a volume of distribution at steady-state (Vss = 0.72 +/- 0.15 L/kg) lower than normal goats (Vss = 1.19 +/- 0.33 L/kg). The elimination of the drug was also modified. Total plasma clearance (Cl) decreased from 0.24 +/- 0.12 L/kg/h in healthy animals to 0.13 +/- 0.05 L/kg/h in animals with endotoxin-induced fever, which is related to an increase in the area under the plasma concentration-time curve (AUC). Consequently, mean residence time (MRT) was also slightly increased in sick animals (MRT = 5.28 +/- 00.99 and 6.09 +/- 01.45 h, in healthy and febrile animals, respectively).     

The influence of disease on feed and water consumption and on pharmacokinetics of orally administered oxytetracycline in pigs

In the present study the feed and water consumption and pharmacokinetic parameters of orally administered oxytetracycline were compared in clinically healthy pigs and in the same pigs following a challenge with Actinobacillus (Haemophilus) pleuropneumoniae toxins. Endobronchial challenge with A. pleuropneumniae toxins was accompanied by anorexia, increased lassitude, labored breathing, fever, and increased white blood cell counts. Pleuropneumonia was evident in all pigs on autopsy. Following the challenge, both feed and water consumption were markedly reduced. In contrast to recommendations in the literature, it is concluded that drugs should not be administered to pneumonic pigs via water. In healthy pigs the oral bioavailability of oxytetracycline (50 mg/kg), given on an empty stomach, was 4.8% and the elimination half-life (t1/2 beta) was 5.92 h. After challenge, the pigs showed great variation in oxytetracycline plasma concentrations. In addition, the mean computed elimination rate constant (beta), t1/2 beta, the area under the plasma concentration-time curve (AUC), and clearance in pneumonic pigs differed significantly (P less than .05) from the values found in healthy pigs. The elimination half-life (t1/2 beta), AUC, and volume of distribution (Vd area) were increased. In diseased pigs the mean of maximum plasma concentrations (.87 micrograms/ml) was reached after 7 h, in contrast to 1.74 h (1.87 micrograms/ml) in the healthy pigs.     

Investigations on prophylactic effects of coarse feed structure and/or potassium diformate on the microflora in the digestive tract of weaned piglets experimentally infected with Salmonella Derby

The purpose of this study was to examine potential prophylactic effects of a coarse feed structure and/or potassium diformate (KDF as feed additive) addition to diets on the microflora of the digestive tract in reared piglets experimentally infected with Salmonella Derby. The results show that coarse grinding as well as KDF addition are able to influence positively the intestinal flora and are capable to reduce Salmonella excretion of infected piglets. Coarse grinding of main ingredients (e.g. cereals) led to an increased number of lactobacilli as well as to higher counts of Gram-positive coccoid bacteria in the colon chyme, while KDF resulted in a tendency towards lower counts of Escherichia coli within the digestive tract. Moreover, a combination of both treatments influenced the composition of the gastrointestinal flora quite positively. Furthermore, the combination of these dietetic measures resulted in a reduced Salmonella excretion rate, shorter Salmonella shedding period and a reduced translocation of Salmonella within the infected piglets. The positive effects of combining both treatments led to a significantly reduced spreading of Salmonella within the group of pigs, which might be used to diminish Salmonella prevalence in pig production.     

Influence of ruminal distribution on norfloxacin pharmacokinetics in adult sheep

Norfloxacin (NF) ruminal distribution after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration was determined in order to assess the influence of the rumen on the pharmacokinetic behaviour of NF in sheep. Norfloxacin concentrations in rumen were detected after i.v. and i.m. administrations between 4 and 48 h in all animals studied. The experimental distribution ratios after i.v. and i.m. administration expressed as area under the concentration-time curve ratios AUC(rumen)/AUC(plasma) were 0.24 and 0.39, respectively, and thus lower than corresponding predicted value of 5.06. Apparently, drug persisted in the rumen content longer than in plasma. The experimental mean residence time ratios MRT(rumen)/MRT(plasma) after i.v. and i.m. administrations were 2.33 and 1.66, respectively. After p.o. administration, NF concentrations in the rumen content were extremely high compared with the respective plasma concentrations, resulting in mean peak concentrations ratio C(max-rumen)/C(max-plasma) of 383.66 and AUC(rumen)/AUC(plasma) experimental ratio of 402.32. This value was considerably higher (approximately 79 fold) than the predicted distribution ratio of 5.06. Our results suggest that the limited p.o. bioavailability of NF in ruminants could not be attributed to ruminal degradation.     

Tissue distribution and disposition kinetics of enrofloxacin in healthy and E. coli infected broilers

Concentrations of enrofloxacin equivalent activity were determined by microbiological assay in the plasma of healthy and E. coli-infected broilers following single intravenous and oral administrations at 10 mg/kg. Tissue distribution and residue-depletion following multiple oral doses (10 mg/kg for 3 successive days) were investigated. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Plasma enrofloxacin concentrations after intravenous dosing to healthy and infected birds were best described by a two-compartments model. Enrofloxacin concentrations in plasma of infected birds were lower than those of healthy ones. The disposition kinetics of intravenously administered drug in healthy and infected birds were somewhat different. The elimination half-life (t1/2 beta) was 4.75 vs. 3.63 h; mean residence time (MRT) was 6.72 vs 4.90 h; apparent volume of the central compartment (Vc) was 1.11 vs 1.57 l/kg; rate constant for transfer from peripheral to central compartment (k21) was 1.15 vs 1.41 h-1 and total body clearance (ClB) was 0.35 vs 0.53 l/h/kg in healthy and infected birds, respectively. After oral administration, the absorption half-life (t1/2abs) in the infected birds was significantly longer than in healthy birds, while elimination half-life (t1/2el) and MRT were significantly shorter. Bioavailability was higher in infected birds (72.50%) as compared to healthy ones (69.78%). Enrofloxacin was detected in the tissues of healthy and infected birds after daily oral dosing of 10 mg/kg for 3 days. It was more concentrated in liver, kidney, and breast muscle. The minimal inhibitory concentration (MIC) of enrofloxacin against E. coli was 0.064 microgram/ml. On the basis of maintaining enrofloxacin plasma concentrations over the MIC, a dose of 10 mg/kg given intravenously every 20.14 hrs or orally every 20.86 hrs should provide tissue concentrations effective against E. coli infection in chickens.     

Pharmacokinetics and bioavailability of imidocarb dipropionate in swine

A two-way crossover study was performed in eight healthy young pigs to determine the pharmacokinetics of imidocarb dipropionate (IMDP) following intravenous (2 mg/kg b.w.) and intramuscular (2 mg/kg b.w.) administrations. Each animal received one intravenous and one intramuscular injection with a 30-day washout period between the two-treatments. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) assay with UV detector at regular intervals for up to 24 h post-injection. Intravenous plasma concentration profiles best fit a three-compartmental model yielding a mean system clearance (Cl((s))) of 558 mL/kg.h and a mean half-life of 13.91 h. Mean imidocarb AUC((0-infinity)) (microg.h/mL), V(c) (L/kg), V(d(area))(L/kg) and MRT((0-t)) (h) values were 3.58, 0.11, 14.36 and 1.46, respectively. Compartmental modeling of imidocarb, after intramuscular administration produced best fit for two-compartmental model yielding mean Kalpha (h(-1)), Cmax (microg/mL), tmax (h), and bioavailability (%) of 3.89, 2.02, 0.54, and 86.57 for the 2 mg/kg dose level. The present studies showed that IMDP was rapidly absorbed, widely distributed, and slowly eliminated. No adverse effects were observed in any of the pigs after i.v. and i.m. administrations of IMDP. The favorable PK behavior, such as the long half-life, acceptable bioavailability indicated that it is likely to be effective in pigs.     

Effect of withdrawing feed from swine on meat quality and prevalence of Salmonella colonization at slaughter

OBJECTIVE: To determine whether withholding feed from pigs prior to slaughter had any effects on meat quality, percentage of pigs with Salmonella spp in cecal contents during slaughter, or percentage of pigs with lacerations of the gastrointestinal tract during slaughter. DESIGN: Split-plot design. ANIMALS: 873 pigs. PROCEDURES: At the finishing barn, pigs were assigned to 30 pens. Feed withdrawal times were assigned to pens at random, and pigs in each pen were marketed in 3 groups. The first marketing group consisted of the 10 heaviest pigs in each pen, the second consisted of the next 10 heaviest pigs, and the third consisted of all remaining pigs. RESULTS: Withdrawing feed improved the redness score assigned to the meat but did not have any other significant effects on carcass composition or meat quality. The percentage of pigs with Salmonella spp in the cecal contents decreased from the first (73%) to the second (64%) to the third (52%) marketing group. However, isolation of Salmonella spp from cecal contents was not associated with feed withdrawal time or with pen prevalence of Salmonella shedding during the 2 months prior to slaughter. Feed withdrawal time and marketing group did not have any significant effects on overall prevalence of gastrointestinal tract lacerations. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that withdrawal of feed from pigs prior to slaughter does not increase the prevalence of Salmonella colonization or the risk of carcass contamination associated with gastrointestinal tract lacerations during slaughter but only slightly enhances meat quality.     

盐酸头孢噻呋注射液在猪体内的比较药动学研究

本研究采用肺部支气管灌流技术对盐酸头孢噻呋注射液在健康猪和患巴氏杆菌病的感染猪体内的药动学特征进行了比较,为指导盐酸头孢噻呋注射液治疗猪巴氏杆菌病提供临床数据支持。选取12头健康仔猪,随机均分为健康组和感染组。感染组通过人工感染多杀性巴氏杆菌建立疾病模型。2组动物分别按交叉试验设计,肌内注射盐酸头孢噻呋注射液,在不同时间点采集血液和支气管肺泡灌洗液,用高效液相色谱法（HPLC）检测头孢噻呋含量。健康猪血浆及支气管肺泡灌洗液中的药峰浓度（C_max）分别为22.33和2.49 μg/mL,相差近9倍;消除半衰期（T_1/2）分别为19.51和70.19 h,在肺部的消除非常缓慢,时长是血浆的3.6倍;药-时曲线下面积（AUC_0-∞）分别为372.05和94.59 μg·h/mL;表观分布容积（Vd/F）分别为0.41和5.24 L/kg,头孢噻呋与肺脏呈现高度结合。感染组血浆及支气管肺泡液C_max分别为11.81和5.05 μg/mL,T_1/2分别为11.79和24.65 h,AUC_0-∞分别为162.65和29.73 μg·h/mL,Vd/F分别为0.53和4.65 L/kg,与健康组表现出相同的特点。结果表明,盐酸头孢噻呋注射液在猪体内具有吸收迅速,消除缓慢,生物利用度高的药代动力学特点,且其在血浆和支气管肺泡灌洗液中的药动学参数存在显著差异。     

Different feed withdrawal times before slaughter influence caecal fermentation and faecal Salmonella shedding in pigs

The effects of different pre-slaughter feed withdrawal times (FWT) on the gastrointestinal tract (GIT) weight and the gut environment of pigs and Salmonella shedding were investigated. Trial 1 evaluated the effects under experimental conditions (feed withdrawal for 18, 30 and 36 h) and trial 2 under commercial conditions (15 and 30 h). In trial 1, the GIT weight tended to decrease (P=0.07), the caecal pH increased (P<0.0001), short-chain fatty acids (SCFA) decreased (P<0.001) and percentage of branched-chain fatty acids (BCFA) increased as FWT increased. Similar results were observed in trial 2, but Enterobacteriaceae numbers and Salmonella positive pigs tended to increase whereas lactobacilli decreased (P<0.0005) as FWT increased. The increase in FWT involved changes in the gut microbial ecosystem that could be associated with the trend of increased caecal Enterobacteriaceae and Salmonella in faeces, and may represent a higher risk of carcass contamination in cases of laceration of viscera.     

Drug residues in food animals II. Plasma and tissue kinetics of oxytetracycline in young cross-bred swine

Tissue distribution and elimination kinetics of oxytetracycline in sixteen organs and body fluids were determined in young pigs following intravenous and oral administration. Seventeen non-fasted pigs, 8–10 weeks of age, weight range 16.4–34.5 kg were dosed intravenously at a dose rate of 11 mg/kg bodyweight. An additional seventeen weaning pigs, 12–14 weeks of age, weight range 27.2–36.3 kg were dosed orally at a dose rate of 48–65 mg/kg bodyweight. Oxytetracycline was rapidly distributed (half-life, 6.71 ± 1.13 min) in swine. The mean volume of distribution was 1.26 ± 0.18 l/kg and overall body clearance was 3.82 ± 0.59 ml/kg/min. The elimination half-life of oxytetracycline in pigs was 3.87 ± 0.62 h, which is shorter than has been observed in other domestic animal species. Oxytetracycline became rapidly and efficiently involved in enterohepatic cycling, with as much as 70% of a total intravenous dose being available for reabsorption from the gastrointestinal tract within 1 h after administration. This high degree of enterohepatic recycling prolonged the half-life, and the large amount of drug that entered the enteric tract contributed to the high volumes of distribution and high k ₁₂/ k ₂₁ ratios. The excellent tissue penetration of this drug further contributed to the high volume of distribution and high k ₁₂/ k ₂₁ ratios obtained. Relationships between plasma and tissue depletion for several major edible organs were found to be statistically significant. Blood plasma is proposed as a body fluid for monitoring oxytetracycline tissue residues.     

Effect of fructo‐oligosaccharides on nutrient digestibility and digesta retention time in adult guinea pigs

A previous study suggested that addition of fructo‐oligosaccharides (FOS) to the diet improved nitrogen (N) utilization and decreased acid detergent fiber (ADF) digestibility in guinea pigs. The present study was conducted to clarify the relationship between ADF digestibility and gastrointestinal mean retention time (MRT) in guinea pigs under FOS supplementation. Adult male guinea pigs were fed a commercial diet (50 g/day) with either 5% glucose (glucose group) or 5% FOS (FOS group) for 12 days in individual metabolism cages. Unlike the glucose group, N utilization improved, but ADF digestibility significantly (P < 0.05) decreased in the FOS group. MRT of solid digesta also significantly (P < 0.05) decreased in the FOS group compared with that in the glucose group. We concluded that reduction of MRT of solid digesta containing FOS decreased ADF digestibility in guinea pigs.     

Plasma achiral and chiral pharmacokinetic behaviour of intravenous oxfendazole co-administered with piperonyl butoxide in sheep

Co-administration of piperonyl butoxide (PB) potentiates fenbendazole (FBZ) in small ruminants. The resultant increase in bioavailability of FBZ and its metabolite oxfendazole (OFZ) has important implications for the efficacy of these drugs against benzimidazole (BZD)-resistant strains of Teladorsagia circumcincta. This study evaluated the racemic (achiral) and enantiomeric (chiral) plasma disposition kinetics of OFZ and its metabolites after the co-administration of PB and OFZ in sheep. Six 6-8-month-old, parasite-free, female Dorset sheep (30-40 kg) were used in a two-phase crossover experiment. In phase I, three sheep received 30 mg/kg PB orally, followed by a single intravenous (i.v.) injection of OFZ at 5 mg/kg. The other three animals were treated similarly except that 5 mL of water replaced PB. In phase 2, treatments for the two groups were reversed and were given 14 days after the initiation of phase I. Three analytes OFZ, FBZ and fenbendazole sulphone (FBZSO(2)) were recovered in plasma up to 48 h post-treatment in both experimental groups. Achiral and chiral pharmacokinetic (PK) profiles for OFZ, after the co-administration of PB, were characterized by a significantly greater area under the concentration--time curve (AUC) and a longer mean residence time (MRT). Chiral OFZ distribution ratios were comparable in both treatment groups. Piperonyl butoxide treatment markedly influenced the plasma PK profiles for FBZ and FBZSO(2) following OFZ administration. Production of FBZ was enhanced as reflected by increased (> 60%) AUC, delayed T(max) and a significantly delayed (> 45%) elimination (t(1/2)(el)). Although AUC values for FBZSO(2) were not significantly different between groups, this metabolite was depleted more slowly from plasma (t(1/2)(el) > 60% and MRT > 42%) following PB treatment. This study demonstrated that PB co-administration is associated with an inhibition of OFZ biotransformation, as evidenced by the significantly higher plasma concentrations of OFZ and FBZ, and this could have important implications in terms of anti-parasite therapy against BZD-resistant parasite strains.     

Plasma concentrations of endothelin-like immunoreactivity in healthy horses and horses with naturally acquired gastrointestinal tract disorders

OBJECTIVE: To compare plasma endothelin (ET)- like immunoreactivity between healthy horses and those with naturally acquired gastrointestinal tract disorders. ANIMALS: 29 healthy horses and 142 horses with gastrointestinal tract disorders. PROCEDURE: Blood samples were collected from healthy horses and from horses with gastrointestinal tract disorders prior to treatment. Magnitude and duration of abnormal clinical signs were recorded, and clinical variables were assessed via thorough physical examinations. Plasma concentrations of ET-like immunoreactivity were measured by use of a radioimmunoassay for human endothelin-1, and CBC and plasma biochemical analyses were performed. RESULTS: Plasma ET-like immunoreactivity concentration was significantly increased in horses with gastrointestinal tract disorders, compared with healthy horses. Median plasma concentration of ET-like immunoreactivity was 1.80 pg/ml (range, 1.09 to 3.2 pg/ml) in healthy horses. Plasma ET-like immunoreactivity was greatest in horses with strangulating large-intestinal obstruction (median, 10.02 pg/ml; range, 3.8 to 22.62 pg/ml), peritonitis (9.19 pg/ml; 789 to 25.83 pg/ml), and enterocolitis (8.89 pg/mI; 6.30 to 18.36 pg/ml). Concentration of ET-like immunoreactivity was significantly associated with survival, PCV, and duration of signs of pain. However, correlations for associations with PCV and duration of pain were low. CONCLUSIONS AND CLINICAL RELEVANCE: Horses with gastrointestinal tract disorders have increased plasma concentrations of ET-like immunoreactivity, compared with healthy horses. The greatest values were detected in horses with large-intestinal strangulating obstructions, peritonitis, and enterocolitis. This suggests a potential involvement of ET in the pathogenesis of certain gastrointestinal tract disorders in horses.     

A Pilot Study Exploring the Relationship Between Digesta Retention Time in the Equine Gastrointestinal Tract and Compartment Models

Digesta retention time within specific segments of the equine gastrointestinal tract (GIT) may be more relevant to scientific inquiries than total tract mean retention time (TTMRT); however, measuring retention time in individual segments requires access to the digestive tract. The objective of this study was to compare prececal, cecal, and colonic mean retention time (MRT) with model-derived compartment MRT. A cecally fistulated gelding was fed indigestible particulate and liquid markers to determine TTMRT and dosed with different pairs of particulate and liquid markers into the cecum (hindgut MRT) and into the right ventral colon through the cecocolic orifice (colon MRT). Fecal marker concentrations were fit to stochastic and mechanistic models using nonlinear least squares methods (MATLAB). Total tract MRT and MRT for each GIT segment were compared with model-derived compartment MRT using paired t-test to determine differences and two one-sided tests to determine equivalence. All models resulted in parameter estimates and an acceptable fit to fecal marker excretion curves, but some parameter estimates did not differ from zero (95% CI included 0). Model-derived TTMRT were equivalent (P < .05) to arithmetically calculated MRT. Most GIT segment MRT differed (P < .05) from model-derived compartment MRT. Differences ranged from −26.1 hours to 25.8 hours. In these exploratory data, model derived compartment retention times failed to pair with MRT in different GIT segments. Significant methodological and analytical challenges remain to describe retention time in individual segments of the equine GIT.     

The influence of Actinobacillus pleuropneumoniae infection on tulathromycin pharmacokinetics and lung tissue disposition in pigs

A tulathromycin concentration and pharmacokinetic parameters in plasma and lung tissue from healthy pigs and Actinobacillus pleuropneumoniae (App)‐infected pigs were compared. Tulathromycin was administered intramuscularly (i.m.) to all pigs at a single dose of 2.5 mg/kg. Blood and lung tissue samples were collected during 33 days postdrug application. Tulathromycin concentration in plasma and lung was determined by high‐performance liquid chromatography with tandem mass spectrometry (LC‐MS/MS) method. The mean maximum plasma concentration (C_max) in healthy pigs was 586 ± 71 ng/mL, reached by 0.5 h, while the mean value for C_max of tulathromycin in infected pigs was 386 ± 97 ng/mL after 0.5 h. The mean maximum tulathromycin concentration in lung of healthy group was calculated as 3412 ± 748 ng/g, detected at 12 h, while in pigs with App, the highest concentration in lung was 3337 ± 937 ng/g, determined at 48 h postdosing. The higher plasma and lung concentrations in pigs with no pulmonary inflammation were observed at the first time points sampling after tulathromycin administration, but slower elimination with elimination half‐life t_1/2el = 126 h in plasma and t_1/2el = 165 h in lung, as well as longer drug persistent in infected pigs, was found.     

Pharmacokinetics of sarafloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications

Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analysed by a noncompartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t1/2beta) were 3.37 +/- 0.46, 4.66 +/- 1.34, 7.20 +/- 1.92 (pigs) and 2.53 +/- 0.82, 6.81 +/- 2.04, 3.89 +/- 1.19 h (broilers), respectively. After i.m. and p.o. doses, bioavailabilities (F) were 81.8 +/- 9.8 and 42.6 +/- 8.2% (pigs) and 72.1 +/- 8.1 and 59.6 +/- 13.8% (broilers), respectively. Steady-state distribution volumes (Vd(ss)) of 1.92 +/- 0.27 and 3.40 +/- 1.26 L/kg and total body clearances (ClB) of 0.51 +/- 0.03 and 1.20 +/- 0.20 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), mean residence times (MRT), and mean absorption times (MAT) were also determined. Sarafloxacin was demonstrated to be more rapidly absorbed, more extensively distributed, and more quickly eliminated in broilers than in pigs. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 10 mg/kg given intramuscularly every 12 h in pigs, or administered orally every 8 h in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 microg/mL.     

Comparison of pharmacokinetics of danofloxacin and enrofloxacin in calves challenged with Mannheimia haemolytica

OBJECTIVE: To compare concentrations of danofloxacin, enrofloxacin, and ciprofloxacin in plasma and respiratory tissues of calves treated after challenge with Mannheimia haemolytica. ANIMALS: 75 calves. PROCEDURE: 24 hours after challenge with M. haemolytica, 72 calves with clinical signs of respiratory tract disease were randomly assigned to 1 of 12 equal treatment groups.Three nonchallenged, nontreated calves formed a control group. Challenged calves were treated with danofloxacin (6 and 8 mg/kg, SC) and enrofloxacin (8 mg/kg, SC) once. At 1, 2, 6, and 12 hours after treatment, 6 calves from each treatment group were euthanatized. Antimicrobial drug concentrations were assayed in various specimens. Peak plasma concentration (Cmax)-to-minimum inhibitory concentration (MIC; Cmax-to-MIC) ratios and the area under the concentration versus time curve over a 12-hour period-to-MIC ratios (AUC(12h)-to-MIC) were calculat-ed. RESULTS: Danofloxacin and enrofloxacin had MICs of 0.03 microg/mL for the M. haemolytica challenge isolate. Danofloxacin administered at doses of 6 and 8 mg/kg resulted in numerically higher geometric mean concentrations of danofloxacin in plasma and all respiratory tissues than geometric mean concentrations of enrofloxacin after treatment with enrofloxacin. Geometric mean concentrations of enrofloxacin were numerically higher than geometric mean concentrations of ciprofloxacin metabolite in plasma and almost all respiratory tissues. Danofloxacin and enrofloxacin achieved Cmax-to-MIC ratios >10 and AUC(12h)-to-MIC ratios >125 hours. CONCLUSIONS AND CLINICAL RELEVANCE: When used to treat pneumonic pasteurellosis in calves, danofloxacin and enrofloxacin can be expected to deliver concentration-dependent bactericidal activity against M. haemolytica, the bacteria most commonly associated with bovine respiratory tract disease.