Treatment of canine pyoderma with ibafloxacin and marbofloxacin--fluoroquinolones with different pharmacokinetic profiles

Dogs with superficial or deep pyoderma (n = 228) presented to first opinion veterinarians (n = 20) were treated orally with either ibafloxacin, at a dosage of 15 mg/kg, or marbofloxacin, at a dosage of 2 mg/kg, once daily for 3-16 weeks. On initial presentation, 35% of the cases were classified as having recurrent pyoderma and 40% as having deep pyoderma. Staphylococci (mainly Staphylococcus intermedius) were isolated from over 90% of the cases. The average treatment periods were 41 +/- 26 and 38 +/- 21 days in the ibafloxacin and marbofloxacin groups, respectively. One week after the cessation of treatment, 74 and 81% of dogs (P > 0.05) in the ibafloxacin and marbofloxacin groups, respectively, were classified as having responded to treatment. One month after the cessation of treatment, 70% of the dogs in each group were still classified as cured or improved, and 3 and 11% (P < 0.05) in the ibafloxacin and marbofloxacin groups, respectively, were classified as having relapsed. Despite having different pharmacokinetic profiles, ibafloxacin and marbofloxacin produced similar results when used under field conditions at the recommended dosages.     

维康对肥育猪的饲喂试验

本研究旨在观察比较不同饲料添加剂对肥育猪生产性能的影响。选用体重20 kg左右的杜长大三元杂交（杜洛克×长白×大约克）瘦肉型商品猪100头,随机分为5组,每组设2个重复,每个重复10头。每组使用相同基础日粮,分别使用四种不同饲料药物添加剂进行了饲喂试验,即在基础饲粮中添加A组喹烯酮25%预混料300 mg/kg、B组维康200 mg/kg、C组维康300 mg/kg、D组北里霉素10%预混料300mg/kg的添加剂,空白对照组不添加任何添加剂。饲养时间为83 d。本试验饲养效果观察结果表明：全期日增重试验A、D组和空白对照组差异不显著（p〉0.05）,B、C组和空白对照组差异显著（p〈0.05）,B组维康按照200 mg/kg添加日增重最高,饲料报酬最高,经济效益最好。     

Clinical efficacy of intravenous administration of marbofloxacin in a Staphylococcus aureus infection in tissue cages in ponies

Tissue cages (TC), implanted subcutaneously in the neck in eight ponies, were inoculated with Staphylococcus aureus (S. aureus) to determine the clinical efficacy of marbofloxacin in the treatment of this infection. From 21 h after inoculation, marbofloxacin (6 mg/kg) was administered intravenously (i.v.) once daily for 7 days. Samples of the tissue cage fluid (TCF) were taken to determine marbofloxacin concentrations (days 1, 3 and 7), using high-pressure liquid chromatography, and numbers of viable bacteria [colony forming units (CFU)] (days 1, 3, 7, 14 and 21). Statistical analysis was used to compare CFU before and after treatment. Clinical signs and CFU were used to evaluate the efficacy of treatment. Although, there was a slight decrease in CFU in all TC initially, the infection was not eliminated by marbofloxacin treatment in any of the ponies and abscesses formed. As the MIC (0.25 microg/mL) did not change during treatment and the concentration of marbofloxacin during treatment (mean concentration in TCF was 0.89 microg/mL on day 1, 0.80 microg/mL on day 3 and 2.77 microg/mL on day 7) was above MIC, we consider that the treatment failure might be attributable to the formation of a biofilm by S. aureus. Based on the present results, i.v. administration of marbofloxacin alone is not suitable for the elimination of S. aureus infections from secluded sites.     

Pharmacokinetic characteristics and tissue residues for marbofloxacin and its metabolite N-desmethyl-marbofloxacin in broiler chickens

OBJECTIVES: To determine pharmacokinetic characteristics of marbofloxacin after a single IV and oral administration and tissue residues after serial daily oral administration in chickens. ANIMALS: 40 healthy broiler chickens. PROCEDURE: Two groups of chickens (groups A and B; 8 chickens/group) were administered a single IV and oral administration of marbofloxacin (2 mg/kg). Chickens of group C (n = 24) were given serial daily doses of marbofloxacin (2 mg/kg, PO, q 24 h for 3 days). Plasma (groups A and B) and tissue concentrations (group C) of marbofloxacin and its major metabolite N-desmethyl-marbofloxacin were determined by use of high-performance liquid chromatography. Residues of marbofloxacin and N-desmethylmarbofloxacin were measured in target tissues. RESULTS: Elimination half-life and mean residence time of marbofloxacin in plasma were 5.26 and 4.36 hours after IV administration and 8.69 and 8.55 hours after oral administration, respectively. Maximal plasma concentration was 1.05 microg/ml, and interval from oral administration until maximum concentration was 1.48 hours. Oral bioavailability of marbofloxacin was 56.82%. High concentrations of marbofloxacin and N-desmethyl-marbofloxacin were found in the kidneys, liver, muscles, and skin plus fat 24 hours after the final dose of marbofloxacin; however, marbofloxacin and N-desmethyl-marbofloxacin were detected in only hepatic (27.6 and 98.7 microg/kg, respectively) and renal (39.7 and 69.1 microg/kg, respectively) tissues 72 hours after termination of marbofloxacin treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of pharmacokinetic data obtained in this study reveals that a minimal therapeutic dose of 2 mg/kg, PO, every 24 hours should be appropriate for control of most infections in chickens.     

Effects of growth hormone administration on vitamin D metabolism and vitamin D receptors in the pig

Twelve 36-kg pigs were given either 100 micrograms/kg porcine pituitary growth hormone (pGH) or placebo injections daily for 33 days. Serum was obtained weekly for analysis of minerals and vitamin D metabolites. On day 34, the pigs were sacrificed and renal and duodenal tissue were obtained for analysis of vitamin D receptor content (VDR). Animals treated with pGH grew faster and had a higher rate of bone accretion than did control animals. Serum concentrations of 1,25-dihydroxyvitamin D (1,25-(OH)2D) were significantly higher in pGH-treated pigs than in control pigs at all time points following initiation of treatment, with the greatest difference observed at day 28 (42.4 +/- 4.9 pg/ml in controls vs. 65.4 +/- 4.7 pg/ml in pGH-treated pigs). Serum 24,25-dihydroxy-vitamin D tended to be lower in pGH-treated pigs than in control pigs, being significantly lower on day 21 of the experiment (3.22 +/- .52 vs. 6.73 +/- 1.22 ng/ml, respectively). Serum concentrations of 25-hydroxyvitamin D and calcium were unaffected by pGH treatment. Kidneys of control pigs contained significantly more unoccupied vitamin D receptors than did kidneys from pGH-treated pigs (73.3 +/- 4.3 vs. 58.3 +/- 4.1 fmoles/mg protein). Duodenal tissue unoccupied vitamin D receptor content was similar in both pGH-treated (245 +/- 17.9 fmoles/mg protein) and control (263 +/- 21.8 fmoles/mg protein) pigs. Duodenal occupied vitamin D receptor concentration was similar in both pGH-treated (6.8 +/- .75 fmoles/mg protein) and control pigs (5.32 +/- .77 fmoles/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of amoxicillin administered in drinking water to recently weaned 3- to 4-week-old pigs with diarrhea experimentally induced by Escherichia coli O149:F4

OBJECTIVE: To measure effects of Escherichia coli O149:F4-induced diarrhea on water consumption and pharmacokinetics of amoxicillin after administration in drinking water. ANIMALS: 24 recently weaned 24- to 28-day-old crossbred pigs. PROCEDURE: 10 pigs were inoculated with E. coli O149:F4; all 10 pigs subsequently developed diarrhea. Pigs were medicated by administration of amoxicillin in the drinking water (0.75 mg/mL) for a 4-hour period on 2 consecutive days. Fourteen age-matched noninfected healthy pigs (control group) were medicated in a similar manner. Blood samples were obtained from both groups daily, and plasma concentrations of amoxicillin were analyzed by use of high-performance liquid chromatography. RESULTS: Diarrhea reduced the area under the plasma concentration-versus-time curve (AUC) and maximum plasma concentration (C(max)) of amoxicillin on the first day of medication by 56% and 63%, respectively. The AUC of amoxicillin on the second day of medication for diarrheic pigs did not differ significantly from that of control pigs on the first day of medication. CONCLUSIONS AND CLINICAL RELEVANCE: E. coli-induced diarrhea reduced the AUC of amoxicillin and time that plasma concentration of amoxicillin was > 0.025 microg/mL and, hence, less likely to have a therapeutic effect on the first day of administration in drinking water. On the assumption that plasma concentrations may indirectly reflect concentrations at the site of infection, analysis of our results suggests that higher doses of amoxicillin may be appropriate for administration in drinking water during a 4-hour period on the first day that pigs have diarrhea attributable to E. coli O149:F4.     

二氟沙星对实验性感染猪链球菌病及支原体性肺炎的药效学研究

本文报道国内新近研制的畜禽专用氟喹诺酮类抗菌药物－二氟沙星对实验性感染猪链球菌病及支原体性肺炎的药效学研究。以试管两倍稀释法测得二氟沙星对兰氏C群类马链球菌（C55120）和猪肺炎支原体（F16株）的最小抑菌浓度（MIC）分别是1．6级及0．16mg/L。肌注给药对猪链球菌病和支原体性肺炎的实验性治疗结果表明，低、中、高剂量二氟沙星组（2．5、5、10mg/kg)及恩诺沙星组（2．5mg/kg)用药5d（每隔12h给药1次）对猪链球菌病的治愈分别是40％、70％、80％及70％，而链球菌感染对照组的死亡率为70％；低、中、高剂量二氟沙星组及恩诺沙星组（2．5mg/kg)用药5d（每隔12h给药1次）对猪支原体性肺炎的治愈率分别是80％、90％、90％及80％；而支原体感染对照组的自愈率为10％。     

Exposure time-dependent bactericidal activities of amoxicillin against Actinobacillus pleuropneumoniae; an in vitro and In vivo pharmacodynamic model

The pharmacodynamic effects of amoxicillin against Actinobacillus pleuropneumoniae at exposure concentration above and below minimum inhibitory concentration (MIC) were evaluated in both in vitro and in vivo. In vitro, the growth and morphological change of A. pleuropneumoniae in culture medium was observed. In vivo, the efficacy of amoxicillin on experimentally induced A. pleuropneumoniae infection in disease-free pigs was evaluated. Fifteen pigs were divided into three groups (n = 5 per group). After the onset of clinical respiratory disease symptoms, 6 h post-infection, amoxicillin sustained-release injectable formulation was injected intramuscularly at 7.5 mg/kg/day (group I) and 15 mg/kg/day (group II). Then the serum concentration of amoxicillin was measured. An untreated infected group served as controls. In each amoxicillin administration group, if symptoms were not absent after 48 h, the pig was injected with the amoxicillin sustained-release injectable formulation again using the same dosage. In vitro, the growth of A. pleuropneumoniae inhibited by amoxicillin exposure at the concentration above the MIC (1.28 x MIC), and the inhibition time was in directly proportion to the time of amoxicillin exposure. Moreover, all the cells were lysed. Whereas the bacterial growth inhibition at the amoxicillin exposure concentration below the MIC (0.25 x MIC) was not done, and the shape of cells were normal or long filamentous. In vivo, the group I clinical and pathological score was higher than the group II, and the group I weight gain was significantly less than the group II. Performance with respect to weight gain corresponded with clinical signs. The infected control group was severely affected with an 80% (4/5) mortality rate 24-96 h post-challenge. The duration of time above MIC (T > MIC) of serum amoxicillin concentration in the group I was less than group II. The present studies suggest that amoxicillin has exposure time-dependent bactericidal activity against A. pleuropneumoniae.     

Therapy of difficult cases of canine pyoderma with marbofloxacin: a report of 39 dogs

Thirty-nine dogs with severe and/or recurrent lesions of pyoderma were treated with marbofloxacin at an average dosage of 2.12 mg/kg bodyweight, once daily, for time periods varing from 10 to 213 days. Forty-seven strains of bacteria, isolated from 34 cultures, were tested for sensitivity to various antibiotics. At day 0, no resistance to marbofloxacin was found, but one refractory case, a strain of Staphylococcus intermedius resistant to marbofloxacin, was cultured at day 28. Thirty-three dogs (84.6 per cent) showed an excellent response (cure), one (2.6 per cent) a clear improvement and one (2.6 per cent) a smaller improvement, while the remaining four dogs showed no response after 11 to 60 days. Fifteen dogs (45.5 per cent) relapsed over the follow-up period of three to 191 days, but none of the dogs in the study exhibited any adverse effects.     

Efficacy of tulathromycin injectable solution for the treatment of naturally occurring Swine respiratory disease

Tulathromycin, a novel triamilide antimicrobial, was evaluated for treatment of swine respiratory disease (SRD) in field efficacy studies involving 720 pigs in six North American swine herds. In each study, feeder pigs with clinical SRD were randomly assigned in equal numbers to a group treated with tulathromycin given as a single injection at 2.5 mg/kg of body weight or to a saline-treated control group. Four of the studies included a third group treated with ceftiofur sodium for 3 consecutive days at 3 mg/kg of body weight. Pigs were treated on day 0 and evaluated for treatment response on day 7. In each study, 10 or more nontreated pigs and saline-treated pigs that did not respond to treatment underwent necropsies to obtain lung samples that were evaluated for SRD pathogens. The overall cure rate was 46.4% for saline-treated pigs, 71.1% for tulathromycin-treated pigs, and 63.1% for ceftiofur-treated pigs. The cure rate for tulathromycin-treated pigs was significantly higher than for saline-treated pigs (P = .0116). Mortality from SRD occurred in 24 control pigs, seven tulathromycin-treated pigs, and one ceftiofur-treated pig. The mortality rate was significantly lower for both the tulathromycin- and ceftiofur-treated pigs compared with those treated with saline (P = .0148 and P = .0195, respectively). Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Mycoplasma hyopneumoniae, bacteria commonly associated with SRD, were isolated from SRD-affected pigs. Under field conditions, tulathromycin injectable solution given as a single IM dose of 2.5 mg/kg of body weight was safe and effective in the treatment of SRD.     

First experience on the effect of in-feed lincomycin for the control of proliferative enteropathy in growing pigs

This trial's aim was to evaluate the effect of in-feed lincomycin for the control of proliferative enteropathy (PE; also known as ileitis) in growing pigs, in which it is associated with significant morbidity levels. Investigation regarding the efficacy of this substance in growing pigs has never been carried out before in a field trial. The trial farm had a previous history of PE outbreaks. On day 1 of the trial (age of 62 +/- 1.5 days), 240 pigs were divided into two groups of 120 pigs/group which were allocated into five pens of 24 pigs each. Therefore, a randomized block design was used with two experimental groups (T1-T2) and five replicates (pens) per group. T1 group served as negative control (NC) animals which were receiving no medication and conversely T2 group received in-feed lincomycin at the dose of 110 mg/kg of feed. The treatment period lasted for 3 weeks, followed by an observation period of 4 weeks up to the age of 111 +/- 1.5 days which was the end of the grower stage. Administration of lincomycin at a dose of 110 mg/kg of feed had beneficial effects compared with the NC group. The pigs of T2 group showed significant improvement of their production parameters in terms of average daily body gain (ADG) and feed conversion ratio (FCR) not only during the treatment period (ADG: 0.515 +/- 0.050 versus 0.481 +/- 0.071 and FCR: 2.38 +/- 0.05 versus 2.56 +/- 0.08, for T2 and T1 groups respectively), but also during the remaining period until the end of the grower stage (observation period: ADG: 0.687 +/- 0.019 versus 0.646 +/- 0.044 and FCR: 2.58 +/- 0.02 versus 2.74 +/- 0.02 respectively). Other effects in the T2 group refer to the reduction of diarrhoea prevalence (mean pen diarrhoea score during the whole grower stage: 0.200 +/- 0.060 versus 0.632 +/- 0.041 respectively), morbidity rates (morbidity rates during the whole grower stage: 15.83% versus 45.00% respectively) and the reduction of Lawsonia intracellularis prevalence as shown by polymerase chain reaction diagnostic method (at the end of the treatment period: 10.0% versus 60.0% respectively). In conclusion, treatment with 110 mg lincomycin/kg of feed for 21 consecutive days had a beneficial effect on the control of PE in growing pigs.     

The effect of orally administered marbofloxacin on the pharmacokinetics of theophylline

As certain quinolones can interfere with the metabolism of theophylline by competitive inhibition of the hepatic microsomal cytochrome P450 system, concomitant use of these drugs with theophylline could result in theophylline toxicity. This study investigated the effect of orally administered marbofloxacin (2 and 5 mg/kg each once daily) on steady-state plasma pharmacokinetics of theophylline after concomitant oral administration of a sustained release theophylline preparation in dogs. Marbofloxacin caused some alteration in theophylline metabolism. A 2 mg/kg dose of marbofloxacin did not clearly result in an increased area under the concentration--time curve (AUC) or decreased clearance of theophylline, but at a dose of 5 mg/kg, a statistically significant increase in AUC and a decrease in the total clearance of theophylline was found. The 26% reduction in theophylline clearance is probably not clinically significant in healthy dogs, but for dogs with renal impairment, there might be a chance of theophylline accumulation when dosed concomitantly with marbofloxacin.     

Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality,influence of the age of the animals and urinary elimination

The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl^®). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27‐week‐old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16‐week‐old male pigs. An additional group of 12‐week‐old weaned piglets was used for the evaluation of age‐related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27‐week‐old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed C_max was 6.30 μg/mL, and the AUC_INF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4–16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively.     

阿米卡星脂质体对猪肺疫的疗效试验

为研究阿米卡星脂质体的临床疗效,对10例被诊断为患猪肺疫（猪巴氏杆菌病）的仔猪进行了疗效试验。将患猪随机分为3组,空白对照组肌肉注射生理盐水;药物对照组肌肉注射阿米卡星,剂量为7．5mg／kg,每天用药2次,连用5d;试验药物组肌注阿米卡星脂质体,剂量为5．0mg／kg,每天用药1次,连用3d。结果表明,阿米卡星脂质体组治愈率和有效率分别为70．0％和76．0％,疗效显著高于药物对照组（P〈0．01）。     

Feed supplemented with 3 different antibiotics improved food intake and decreased the activation of the humoral immune response in healthy weaned pigs but had differing effects on intestinal microbiota

The aim of this study was to determine the effects of 3 antibiotics used for pulmonary pathologies added in the feed of weaned pigs on growth performance, commensal microbiota, and immune response. At weaning, a total of 72 pigs were randomly assigned by BW and litter to 1 of the following diets: control (typical weaning diet), control + 400 mg of tilmicosin/kg, control + 600 mg of amoxicillin/kg, and control + 300 mg of doxycycline/kg. Individually penned pigs were slaughtered after 3 wk (12 pigs/treatment) or 4 wk (6 pigs/treatment). During the fourth week, all pigs received the control diet to test the residual effect of the antimicrobial supplementation. The antibiotic supplementation increased growth and feed intake during the first week (P < 0.01) and over the first 3 wk combined (P < 0.05). Gain-to-feed ratio tended to improve during the first week (P = 0.076) by the antibiotics compared with the control. Among the antibiotic treatments, no difference was observed in ADG and feed intake, which were also unchanged by the diet in the fourth week. The fecal enterobacteria counts were increased by amoxicillin on d 14 and 21 (P < 0.05 and 0.01, respectively) and were decreased by tilmicosin (P < 0.001) compared with the control. Amoxicillin decreased lactic acid bacteria (P < 0.01) counts compared with the control. The antibiotic supplementation tended to decrease total bacteria variability in the jejunum (Shannon index, P = 0.091) compared with the control. The antibiotic treatment decreased the mean total serum IgM concentration (P = 0.016) after 3 wk and did not change the mucosal histomorphometry of the small intestine. For tilmicosin, the observed positive action on piglet performance and feed intake can originate by the decreased costs of immune activation determined by the action on intestinal microbiota. For amoxicillin and doxycycline, the observation on intestinal and fecal microbiota seems to be not sufficient to explain their growth-promoting effect.     

Absorption of enrofloxacin and marbofloxacin after oral and subcutaneous administration in diseased koalas (Phascolarctos cinereus)

Griffith, J.E., Higgins, D.P., Li, K.M., Krockenberger, M.B., Govendir, M. Absorption of enrofloxacin and marbofloxacin after oral and subcutaneous administration in diseased koalas (Phascolarctos cinereus). J. vet. Pharmacol. Therap. 33 , 595–604. Koalas (n = 43) were treated daily for up to 8 weeks with enrofloxacin: 10 mg/kg subcutaneously (s.c.), 5 mg/kg s.c., or 20 mg/kg per os (p.o.); or marbofloxacin: 1.0–3.3 mg/kg p.o., 10 mg/kg p.o. or 5 mg/kg s.c. Serial plasma drug concentrations were determined on day 1 and again at approximately 2 weeks, by liquid chromatography. The median (range) plasma maximum concentrations (C_max) for enrofloxacin 5 mg/kg s.c. and 10 mg/kg s.c. were 0.83 (0.68–1.52) and 2.08 (1.34–2.96) μg/mL and the median (range) T_max were 1.5 h (1–2) and 1 h (1–2) respectively. Plasma concentrations of orally dosed marbofloxacin were too low to be quantified. Oral administration of enrofloxacin suggested absorption rate limited disposition pharmacokinetics; the median (range) C_max for enrofloxacin 20 mg/kg p.o. was 0.94 (0.76–1.0) μg/mL and the median (range) T_max was 4 h (2–8). Oral absorption of both drugs was poor. Plasma protein binding for enrofloxacin was 55.4 ± 1.9% and marbofloxacin 49.5 ± 5.3%. Elevations in creatinine kinase activity were associated with drug injections. Enrofloxacin and marbofloxacin administered at these dosage and routes are unlikely to inhibit the growth of chlamydial pathogens in vivo.     

A field comparison of the efficacy and tolerance of marbofloxacin in the treatment of bovine respiratory disease

A multicentre, controlled, randomized and blinded trial was carried out in 180 ruminating calves with pyrexia and respiratory sign(s) on nine Belgian, British and French farms. All animals were sampled for pathogenic bacteria before treatment and at failure/relapse. Calves were injected with either marbofloxacin (M) solution [Marbocyl (Laboratoire Vétoquinol, Lure, France) 10%] at 2 mg/kg/24 h for 4 days intravenously on the first day then subcutaneously, or tilmicosin (T) solution (Micotil, Elanco Products Ltd, Basingstoke, Hants, UK) at 10 mg/kg as a single subcutaneous (s.c.) injection. The animals were examined clinically eight times up to day 28. The bacterial pathogens were found to be sensitive to marbofloxacin: for Pasteurella haemolytica the minimum inhibitory concentration (MIC)90 was 0.08 microg/mL and for P. multocida the MIC90 was 0.04 microg/mL. Cure rates at day 4 for group M and group T were 84 vs. 82%, respectively (P > or = 0.05). However, overall clinical score was significantly lower after 1 day in group M (P < 0.05). There was no difference in either relapse rate or average daily weight gain between groups. Marbofloxacin was found to be better tolerated than tilmicosin at the s.c. injection site (77.5 vs. 42.2% calves without local swelling, P=0.001) and was well tolerated when injected intravenously. Marbofloxacin was shown to have comparable but faster efficacy and better local tolerance than tilmicosin in the treatment of bovine respiratory disease (BRD).     

Pharmacokinetics of marbofloxacin in dogs after oral and parenteral administration

Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and 4 mg/kg, according to a three-way crossover design. The same experimental design was used for the subcutaneous (s.c.) route. In addition, a long-term trial involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day for thirteen weeks was carried out. Plasma and urine samples were collected during the first two trials, plasma and skin samples were collected after the second of these trials. Plasma, urine and skin concentrations of marbofloxacin were determined by a reverse phase liquid chromatographic method. Mean pharmacokinetic parameters after i.v. administration were the following: t1/2β=12.4h; Cl _B= 0.10 L/h.kg; V _area= 1.9 L/kg. The oral bioavailability of marbofloxacin was close to 100% for the three doses. At 2 mg/kg, C _max of 1.4 μg/mL was reached at t _max of 2.5 h. Mean AUC and C _max values had a statistically significant linear relationship with the doses administered. About 40% of the administered dose was excreted in urine as unchanged parent drug. After s.c. administration, the calculated parameters were close to those obtained after oral administration, except t _max (about 1 h) which was shorter. The mean skin to plasma concentration ratio after the long-term trial was 1.6, suggesting good tissue penetration of marbofloxacin.     

Exposure Time‐Dependent Bactericidal Activities of Amoxicillin Against Actinobacillus pleuropneumoniae; an In Vitro and In Vivo Pharmacodynamic Model

The pharmacodynamic effects of amoxicillin against Actinobacillus pleuropneumoniae at exposure concentration above and below minimum inhibitory concentration (MIC) were evaluated in both in vitro and in vivo. In vitro, the growth and morphological change of A. pleuropneumoniae in culture medium was observed. In vivo, the efficacy of amoxicillin on experimentally induced A. pleuropneumoniae infection in disease‐free pigs was evaluated. Fifteen pigs were divided into three groups (n = 5 per group). After the onset of clinical respiratory disease symptoms, 6 h post‐infection, amoxicillin sustained‐release injectable formulation was injected intramuscularly at 7.5 mg/kg/day (group I) and 15 mg/kg/day (group II). Then the serum concentration of amoxicillin was measured. An untreated infected group served as controls. In each amoxicillin administration group, if symptoms were not absent after 48 h, the pig was injected with the amoxicillin sustained‐release injectable formulation again using the same dosage. In vitro, the growth of A. pleuropneumoniae inhibited by amoxicillin exposure at the concentration above the MIC (1.28 × MIC), and the inhibition time was in directly proportion to the time of amoxicillin exposure. Moreover, all the cells were lysed. Whereas the bacterial growth inhibition at the amoxicillin exposure concentration below the MIC (0.25 × MIC) was not done, and the shape of cells were normal or long filamentous. In vivo, the group I clinical and pathological score was higher than the group II, and the group I weight gain was significantly less than the group II. Performance with respect to weight gain corresponded with clinical signs. The infected control group was severely affected with an 80% (4/5) mortality rate 24–96 h post‐challenge. The duration of time above MIC (T > MIC) of serum amoxicillin concentration in the group I was less than group II. The present studies suggest that amoxicillin has exposure time‐dependent bactericidal activity against A. pleuropneumoniae.     

Pharmacokinetics and residues of a new oral amoxicillin formulation in piglets: a preliminary study

The pharmacokinetics of amoxicillin (Amx) were determined in pigs following intravenous (IV) administration of a single dose of 15 mg/kg and a single dose of 15 mg/kg of a new oral formulation (Amx-FP containing 10% amoxicillin). Residue studies were performed to determine residues in edible tissues of healthy pigs after chronic oral administration of Amx-FP at a daily dose of 15 mg/kg for five consecutive days. After IV administration, the plasma concentration was characteristic of a two-compartment open model. The main pharmacokinetic variables were: t(1/2lambda(n)), MRT=90.1 min, V(darea)=0.81 L/kg and Cl(b)=3.9 mL/kg/min. After single oral administration the main pharmacokinetic variables were: C(max)=758 mug/L, t(max)=347 min and Cl(b/f)=3.7 mL/kg/min for Amx-FP. The oral bioavailability (F) was calculated at 11% for Amx-FP. Based on maximum residue levels (MRL) for AMX in pigs established at 50 microg/kg for all tissues, the withdrawal times of AMX in muscle and skin plus fat were estimated (95% tolerance limit and 95% confidence) to fall below the MRL after a withdrawal period of seven days. Levels of AMX in the liver and kidneys were estimated to fall below the MRL after a withdrawal period of four days.