Multidose pharmacokinetics of orally administered florfenicol in the channel catfish (Ictalurus punctatus)

Plasma disposition of florfenicol in channel catfish was investigated after an oral multidose (10 mg/kg for 10 days) administration in freshwater at water temperatures ranging from 24.7 to 25.9 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After the administration of florfenicol, the mean terminal half‐life (t_1/2), maximum concentration at steady‐state (C_ss(max)), time of C_ss(max) (T_max), minimal concentration at steady‐state (C_ss(min)), and V_c/F were 9.0 h, 9.72 μg/mL, 8 h, 2.53 μg/mL, and 0.653 L/kg, respectively. These results suggest that florfenicol administered orally at 10 mg/kg body weight for 10 days could be expected to control catfish bacterial pathogens inhibited in vitro by a minimal inhibitory concentration value of <2.5 μg/mL.     

The pharmacokinetics of dexmedetomidine administered as a constant rate infusion in horses

Dexmedetomidine, the most selective α₂‐adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 μg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography‐mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance from the lower lip of the horse to the ground measured in centimetre. The harmonic mean (SD) plasma elimination half‐life (Lambda z half‐life) for dexmedetomidine was 20.9 (5.1) min, clearance (Cl) was 0.3 (0.20) L/min/kg, and volume of distribution at steady‐state (Vd_ss) was 13.7 (7.9) L/kg. There was a considerable individual variation in the concentration of dexmedetomidine vs. time profile. The level of sedation covaried with the plasma concentration of dexmedetomidine. This implies that for clinical use of dexmedetomidine constant rate infusion in conscious horses, infusion rates can be easily adjusted to effect, and this is preferable to an infusion at a predetermined value.     

Pharmacokinetics of florfenicol in the plasma of Japanese quail

Abstract

AIM: To determine the pharmacokinetics and bioavailability of florfenicol in the plasma of healthy Japanese quail (Coturnix japonica).

METHODS: Sixty-five quail were given an I/V and I/M dose of florfenicol at 30 mg/kg bodyweight (BW). A two-period sequential design was used, with a wash-out period of 2 weeks between the different routes of administration. Concentrations of florfenicol in plasma were determined using high-performance liquid chromatography (HPLC).

RESULTS: A naíve pooled data analysis approach for the plasma concentration-time profile of florfenicol was found to fit a non-compartmental open model. After I/V administration, the mean residence time (MRT), mean volume of distribution at steady state (V_ss), and total body clearance of florfenicol were 12.0 (SD 0.37) h, 8.7 (SD 0.22) L/kg, and 1.3 (SD 0.08) L/h/kg, respectively. After I/M injection, the MRT, mean absorption time (MAT), and bioavailability were 12.3 (SD 0.37) h, 0.2 (SD 0.02) h, and 79.1 (SD 1.79)%, respectively.

CONCLUSIONS: The time for the concentration of florfenicol to fall below the probable effective concentration of 1 µg/ml of approximately 10 h is sufficient for the minimum inhibitory concentration needed for many bacterial isolates. Further pharm acodynamic studies in quail are needed to evaluate a suitable dosage regimen.     

Effect of a potential probiotics Lactococcus garvieae B301 on the growth performance,immune parameters and caecum microflora of broiler chickens

In this study, a novel Lactococcus garvieae B301 was isolated from the intestinal tract of a healthy piglet. L. garvieae B301 was tolerant to acid pH, simulated gastric and small intestinal transit juices, indicating that it was capable of surviving in the gastrointestinal tract. L. garvieae B301 was safe and beneficial to broilers, as broiler chickens supplemented with L. garvieae B301 had lower diarrhoea incidence and mortality than the Control. Moreover, supplementation of broiler diets with L. garvieae B301 resulted in an increase in body weight and the number of caecum lactic acid bacteria and Bifidobacterium spp., and decrease in feed‐to‐gain ratio and the number of caecum coliforms. It also had a positive effect on the thymus index and bursa of Fabricius index and enhanced serum levels of immune globulins. All these results showed that L. garvieae B301 could enhance the growth performance of broiler chickens and improve their health. Thus, L. garvieae B301 could be a promising feed additive for broiler chickens.     

The efficacy of amoxicillin sodium against streptococcosis in cultured olive flounder Paralichthys olivaceus and its pharmacokinetics

The efficacy of amoxicillin sodium for controlling field and experimental Streptococcus iniae and S. parauberis infections in olive flounder (Paralichthys olivaceus) was evaluated after a single intramuscular administration. Furthermore, the minimal inhibitory concentrations (MIC) against 21 Streptococcus strains were determined. In addition, the pharmacokinetics and residue depletion in olive flounder were investigated. Single intramuscular doses of amoxicillin sodium at 20, 40, 80, and 160 mg/kg b.w. fish significantly reduced cumulative mortality rates to 18.8–31.3% (P < 0.05) for S. iniae and to 5.0–15.0% (P < 0.01) for S. parauberis, whereas the S. iniae‐ and S. parauberis‐infected positive control groups showed cumulative mortality rates of 68.8% and 60.0%, respectively. In a S. parauberis outbreak, amoxicillin sodium reduced the cumulative mortality rate to 7.5% and 4.8% at 20 and 40 mg/kg b.w. fish, respectively, whereas that of the untreated control group was 35.2%. Peak plasma concentrations (C_max) following a single intramuscular dose of 40 and 80 mg/kg b.w. fish were 62.64 (T_max, 1.59 h) and 87.61 (T_max, 3.02 h) μg/mL, respectively, with large AUC_0?t/MIC and C_max/MIC ratios, and sufficient T > MIC (time for maintaining plasma drug concentration greater than MICs) for S. iniae and S. parauberis. The estimated withdrawal period of amoxicillin sodium from muscle of olive flounder was about 8 days at 40 mg/kg b.w. fish (at 22 ± 1 °C). These results demonstrated a single intramuscular administration of amoxicillin sodium to be effective against streptococcosis in olive flounder.     

Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK‐PD modeling analysis in pigs

Florfenicol, a structural analog of thiamphenicol, has broad‐spectrum antibacterial activity against gram‐negative and gram‐positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic–pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK‐PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC₅₀ (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time‐killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC_24 hr, AUC_0–∞, T_max, T_1/2, C_max, CL_b, and K_e were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr^?1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr^?1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.     

Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration

The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.) dose was investigated in six camels (Camelus dormedarius). Orphenadrine was extracted from the plasma using a simple sensitive liquid–liquid extraction method and determined by gas chromatography/mass spectrometry (GC/MS). Following i.v. administration plasma concentrations of ORPH decline bi-exponentially with distribution half-life (t_1/2α) of 0.50 ± 0.07 h, elimination half-life (t_1/2β) of 3.57 ± 0.55 h, area under the time concentration curve (AUC) of 1.03 ± 0.10 g/h l⁻¹. The volume of distribution at steady state (Vd_ss) 1.92 ± 0.22 l kg⁻¹, volume of the central compartment of the two compartment pharmacokinetic model (V_c) 0.87 ± 0.09 l kg⁻¹, and total body clearance (Cl_T) of 0.60 ± 0.09 l/h kg⁻¹. Three orphenadrine metabolites were identified in urine samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N-dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl-orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH with molecular ion m/z 285. ORPH and its metabolites in camel were extensively eliminated in conjugated form. ORPH remains detectable in camel urine for three days after i.v. administration of a single dose of 350 mg orphenadrine aspartate.     

Isolation and Pathogenicity of Streptococcus iniae in Cultured Red Hybrid Tilapia in Malaysia

Abstract

This study describes the isolation and pathogenicity of Streptococcus iniae in cultured red hybrid tilapia (Nile Tilapia Oreochromis niloticus × Mozambique Tilapia O. mossambicus) in Malaysia. The isolated gram-positive S. iniae appeared punctiform, transparently white, catalase and oxidase negative and produced complete β-hemolysis on blood agar, while a PCR assay resulted in the amplification of the 16 S rRNA gene and lactate oxidase encoded genes. The isolate was sensitive to tetracycline, vancomycin, and bacitracin but was resistant to streptomycin, ampicillin, penicillin, and erythromycin. Pathogenicity trials conducted in local red hybrid tilapia (mean ± SE = 20.00 ± 0.45 g) showed 90.0, 96.7, and 100.0% mortality within 14 d postinfection following intraperitoneal exposure to 10⁴, 10⁶, and 10⁸ CFU/mL of the pathogen, respectively. The clinical signs included erratic swimming, lethargy, and inappetance at 6 h postinfection, while mortality was recorded at less than 24 h postinfection in all infected groups. The LD_{50-336 h} of S. iniae against the red hybrid tilapia was 10² CFU/mL. The post mortem examinations revealed congested livers, kidneys, and spleens of the infected fish. This is the first report of S. iniae experimental infection in cultured red hybrid tilapia in Malaysia.

Received January 20, 2017; accepted July 16, 2017 Published online October 11, 2017     

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus) at three temperatures after one single intramuscular injection

The pharmacokinetic profiles of florfenicol (FF) or florfenicol amine (FFA) in crucian carp were compared at different water temperatures after single intramuscular administration of FF at 10 mg/kg bodyweight. The concentrations of FF and FFA were determined by a high‐performance liquid chromatography method, and then, the concentration versus time data were subjected to compartmental analysis using a one‐compartment open model. At the water temperatures of 10, 20, and 25°C, the peak concentrations (C_maxs) of FF were 2.28, 2.29, and 2.34 μg/ml, respectively, while those of FFA were 0.42, 0.71, and 0.82 μg/ml, respectively. And the absorption half‐life (t_1/2ka) of FF was 0.21, 0.19, and 0.21 hr, while the elimination half‐life (t_1/2kel) was 31.66, 24.77, and 21.48 hr, respectively. For FFA, the formation half‐life (t_1/2kf) was 3.85, 8.97, and 12.43 hr, while the t_1/2kel was 58.34, 30.27, and 21.22 hr, respectively. The results presented here demonstrated that the water temperature had effects on the elimination of both FF and FFA and the formation of FFA. Based on the T > MIC values calculated here, to treat the infections of bacterial with MIC value ≤ 0.5 μg/ml, FF intramuscularly given at 10 mg/kg bodyweight with a 72‐hr interval is sufficient at the water temperature of 10°C, while the intervals of 60 and 48 hr were needed at 20 and 25°C, respectively. But to treat bacterial with higher MIC values, more FF or FF at 10 mg/kg BW but with shorter intervals should be intramuscularly given to the infected fish.     

Pharmacokinetic profiles of florfenicol in spotted halibut,Verasper variegatus,at two water temperatures

The pharmacokinetic profiles of florfenicol in the spotted halibut (Verasper variegatus) were investigated at 15 and 20°C water temperatures, respectively. Florfenicol content in plasma samples was analyzed using an HPLC method. Drug concentration versus time data were best fitted to a three‐compartment model after a single intravenous administration (15 mg/kg BW), and fitted to a two‐compartment model after an oral administration (30 mg/kg BW) at 15 and 20°C. The florfenicol concentration in the blood increased slowly during the 12 hr following an oral administration at 15°C, with a peak concentration (C_max) of 9.1 mg/L, and then declined gradually. The half‐lives of absorption, distribution, and elimination phase were 2.18, 5.66 and 14.25 hr, respectively. The bioavailability (F) was calculated to be 24.14%. After an oral administration at 20°C, shorter half‐lives of absorption (1.33 hr), distribution (2.51 hr) and elimination (9.71 hr), a higher C_max (12.2 mg/L), and a similar F (23.98%) were found. Based on the pharmacokinetics and pharmacodynamics, an oral dose of 30 mg/kg BW was suggested to be efficacious for bacterial disease control in spotted halibut farming.     

In vitro assessment of chloramphenicol and florfenicol as second‐line antimicrobial agents in dogs

The aim of this study was to evaluate the potential of chloramphenicol and florfenicol as second‐line antimicrobial agents for treatment of infections caused by methicillin‐resistant Staphyococcus pseudintermedius (MRSP) and extended‐spectrum β‐lactamase (ESBL)‐producing Escherichia coli in dogs, through a systematic in vitro assessment of the pharmacodynamic properties of the two drugs. Minimum inhibitory concentrations (MIC) and phenicol resistance genes were determined for 169 S. pseudintermedius and 167 E. coli isolates. Minimum bactericidal concentrations (MBC), time‐killing kinetics, and postantibiotic effect (PAE) of both agents against wild‐type isolates of each species were assessed. For S. pseudintermedius, the chloramphenicol MIC₉₀ was 32 μg/mL. No florfenicol resistance was detected in this species (MIC_90 = 4 μg/mL). The MIC₉₀ of both agents against E. coli was 8 μg/mL. Resistance genes found were cat_pC221 in S. pseudintermedius and catA1 and/or floR in E. coli. The phenicols displayed a time‐dependent, mainly, bacteriostatic effect on both species. Prolonged PAEs were observed for S. pseudintermedius, and no PAEs were detected for E. coli. More research into determination of PK/PD targets of efficacy is needed to further assess the clinical use of chloramphenicol and florfenicol as second‐line agents in dogs, optimize dosage regimens, and set up species‐specific clinical break points.     

Comparative pharmacokinetics of florfenicol in healthy and Pasteurella multocida‐infected Gaoyou ducks

Pasteurella multocida is the causative agent of fowl cholera, and florfenicol (FF) has potent antibacterial activity against P. multocida and is widely used in the poultry industry. In this study, we established a P. multocida infection model in ducks and studied the pharmacokinetics of FF in serum and lung tissues after oral administration of 30 mg/kg bodyweight. The maximum concentrations reached (C_max) were lower in infected ducks (13.88 ± 2.70 μg/ml) vs. healthy control animals (17.86 ± 1.57 μg/ml). In contrast, the mean residence time (MRT: 2.35 ± 0.13 vs. 2.27 ± 0.18 hr) and elimination half‐life (T_½β: 1.63 ± 0.08 vs. 1.57 ± 0.12 hr) were similar for healthy and diseased animals, respectively. As a result, the area under the concentration curve for 0–12 hr (AUC_0–12 hr) for FF in healthy ducks was significantly greater than that in infected ducks (49.47 ± 5.31 vs. 34.52 ± 8.29 μg hr/ml). The pharmacokinetic differences of FF in lung tissues between the two groups correlated with the serum pharmacokinetic differences. The C_max and AUC_0–12 hr values of lung tissue in healthy ducks were higher than those in diseased ducks. The concentration of FF in lung tissues was approximately 1.2‐fold higher than that in serum both in infected and healthy ducks indicating that FF is effective in treating respiratory tract infections in ducks.     

The effect of breed and sex on sulfamethazine,enrofloxacin, fenbendazole and flunixin meglumine pharmacokinetic parameters in swine

Drug use in livestock has received increased attention due to welfare concerns and food safety. Characterizing heterogeneity in the way swine populations respond to drugs could allow for group‐specific dose or drug recommendations. Our objective was to determine whether drug clearance differs across genetic backgrounds and sex for sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine. Two sires from each of four breeds were mated to a common sow population. The nursery pigs generated (n = 114) were utilized in a random crossover design. Drugs were administered intravenously and blood collected a minimum of 10 times over 48 h. A non‐compartmental analysis of drug and metabolite plasma concentration vs. time profiles was performed. Within‐drug and metabolite analysis of pharmacokinetic parameters included fixed effects of drug administration date, sex and breed of sire. Breed differences existed for flunixin meglumine (P‐value<0.05; Cl, Vd_ss) and oxfendazole (P‐value<0.05, AUC_0→∞). Sex differences existed for oxfendazole (P‐value < 0.05; T_max) and sulfamethazine (P‐value < 0.05, Cl). Differences in drug clearance were seen, and future work will determine the degree of additive genetic variation utilizing a larger population.     

The pharmacokinetics of DPH after the administration of a single intravenous or intramuscular dose in healthy dogs

The objective of this study was to determine the pharmacokinetics of diphenhydramine (DPH) in healthy dogs following a single i.v. or i.m. dose. Dogs were randomly allocated in two treatment groups and received DPH at 1 mg/kg, i.v., or 2 mg/kg, i.m. Blood samples were collected serially over 24 h. Plasma concentrations of DPH were determined by high‐performance liquid chromatography, and noncompartmental pharmacokinetic analysis was performed with the commercially available software. Cardio‐respiratory parameters, rectal temperature and effects on behaviour, such as sedation or excitement, were recorded. Diphenhydramine Cl_area, Vd_area and T_1/2 were 20.7 ± 2.9 mL/kg/min, 7.6 ± 0.7 L/kg and 4.2 ± 0.5 h for the i.v. route, respectively, and Cl_area/F, Vd_area/F and T_1/2 20.8 ± 2.7 mL/kg/min, 12.3 ± 1.2 L/kg and 6.8 ± 0.7 h for the i.m. route, respectively. Bioavailability was 88% after i.m. administration. No significant differences were found in physiological parameters between groups or within dogs of the same group, and values remained within normal limits. No adverse effects or changes in mental status were observed after the administration of DPH. Both routes of administration resulted in DPH plasma concentrations which exceeded levels considered therapeutic in humans.     

Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous,subcutaneous and oral administration

The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high‐performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (V_z) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (V_ss) of 0.22 ± 0.12 L/kg. Median plasma terminal half‐life (t_1/2) was 1.19 h (range 0.71–1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C_max 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4–8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5‐hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate.     

Phenotypic and Genotypic Heterogeneity among Streptococcus iniae Isolates Recovered from Cultured and Wild Fish in North America,Central America and the Caribbean Islands

Abstract

Streptococcus iniae, the etiological agent of streptococcosis in fish, is an important pathogen of cultured and wild fish worldwide. During the last decade outbreaks of streptococcosis have occurred in a wide range of cultured and wild fish in the Americas and Caribbean islands. To gain a better understanding of the epizootiology of S. iniae in the western hemisphere, over 30 S. iniae isolates recovered from different fish species and geographic locations were characterized phenotypically and genetically. Species identities were determined biochemically and confirmed by amplification and sequencing of the 16S rRNA gene. Repetitive-element palindromic PCR fingerprinting as well as biochemical and antimicrobial susceptibility profiles suggest that a single strain of S. iniae was responsible for two different disease outbreaks among reef fishes in the Caribbean, one in 1999 and another in 2008. Interestingly, a majority of the isolates recovered from cultured fish in the Americas were genetically distinct from the Caribbean isolates and exhibited a trend toward higher minimal inhibitory concentration with respect to several antibiotics as well as greater genetic variability. The biological significance of this genetic variability is unclear, but it could have implications for future vaccine development and treatment.

Received April 20, 2014; accepted July 7, 2014     

Pharmacokinetics of altrenogest in gilts

Altrenogest, a synthetic progestogen, is characterized by its estrus synchronization in mares, ewes, sows, and gilts. To investigate the pharmacokinetic profile and evaluate its accumulation in gilts, 18 oral doses of 20 mg altrenogest/gilt/day were given to eight healthy gilts at an interval of 24 hr. Plasma samples were collected, and altrenogest was determined by ultra‐high‐performance liquid chromatography with mass spectrometry. WinNonlin 6.4 software was used to calculate the pharmacokinetic parameters through noncompartmental model analysis. After the first administration (D 1), the pharmacokinetic parameters, including T_max, C_max, and the elimination half‐life (T_1/2λz), were similar to those observed after the final administration (D 18). However, the mean residence time at D 1 was significantly lower than D 18. As a whole, the mean steady‐state plasma concentration (C_ss), degree fluctuation (DF), accumulation factor (R_ac), and area under the plasma concentration–time curve in steady state (AUC_ss) were 22.69 ± 6.15 ng/ml, 270.64 ± 42.51%, 1.53 ± 0.23, and 544.63 ± 147.49 ng hr/ml, respectively. These results showed that after 18 consecutive days of oral administration of altrenogest, plasma concentrations of altrenogest had a certain degree of fluctuation, without significant accumulations.     

Mutant prevention concentration,pharmacokinetic–pharmacodynamic integration,and modeling of enrofloxacin data established in diseased buffalo calves

The pharmacokinetic–pharmacodynamic (PK/PD) modeling of enrofloxacin data using mutant prevention concentration (MPC) of enrofloxacin was conducted in febrile buffalo calves to optimize dosage regimen and to prevent the emergence of antimicrobial resistance. The serum peak concentration (C_max), terminal half‐life (t_1/2K₁₀₎, apparent volume of distribution (Vd_(area)/F), and mean residence time (MRT) of enrofloxacin were 1.40 ± 0.27 μg/mL, 7.96 ± 0.86 h, 7.74 ± 1.26 L/kg, and 11.57 ± 1.01 h, respectively, following drug administration at dosage 12 mg/kg by intramuscular route. The minimum inhibitory concentration (MIC), minimum bactericidal concentration, and MPC of enrofloxacin against Pasteurella multocida were 0.055, 0.060, and 1.45 μg/mL, respectively. Modeling of ex vivo growth inhibition data to the sigmoid E_max equation provided AUC_24 h/MIC values to produce effects of bacteriostatic (33 h), bactericidal (39 h), and bacterial eradication (41 h). The estimated daily dosage of enrofloxacin in febrile buffalo calves was 3.5 and 8.4 mg/kg against P. multocida/pathogens having MIC₉₀ ≤0.125 and 0.30 μg/mL, respectively, based on the determined AUC_24 h / MIC values by modeling PK/PD data. The lipopolysaccharide‐induced fever had no direct effect on the antibacterial activity of the enrofloxacin and alterations in PK of the drug, and its metabolite will be beneficial for its use to treat infectious diseases caused by sensitive pathogens in buffalo species. In addition, in vitro MPC data in conjunction with in vivo PK data indicated that clinically it would be easier to eradicate less susceptible strains of P. multocida in diseased calves.     

Pharmacokinetics of sulphadoxine and trimethoprim in sows: Influence of lactation

A potentiated sulpha drug was administered intravenously to 12 sows on the 17th day of lactation and to 4 sows in early pregnancy to study the influence of lactation on its disposition kinetics. The dose-rate of sulphadoxine (SDX) used was 12 mg/kg b.w. while that of trimethoprim (TMP) was 2.4 mg/kg b.w. The pharmacokinetic parameters of SDX showed no significant difference between lactating and pregnant sows (V _ss, 0.24±0.04 L/kg; Cl _s , 0.25±0.05 ml/min per kg: MRT, 17.08±4.48 h). SDX did not accumulate in milk, the concentrations in milk being less than the concentrations in serum at the same time. Of the pharmacokinetic parameters for TMP, only the mean residence time was significantly different between the two groups (V _ss, 1.60±0.31 L/kg; Cl _s , 4.62±1.07 ml/min per kg: MRT_lactating, 5.43±1.26 h; MRT_pregnant, 7.74±1.72 h). TMP was excreted in milk to a considerable extent, the ratio of its concentration in milk to that in serum at the same time being over 2.2. These two substances show a completely different pharmacokinetic behaviour. Even though TMP is excreted more quickly in lactating sows, adjusting the dose of this potentiated sulpha drug does not seem to be appropriate.Abbreviations AUC area under the curve - AUMC area under the first-movement curve - terminal elimination rate constant - b.w. body weight - Cl _s clearance at steady state - D dose - MRT mean residence time - SD standard deviation - SDX sulphadoxine - TMP trimethoprim - V _ss apparent volume of distribution at steady state     

Pharmacokinetics of florfenicol in blunt‐snout bream (Megalobrama amblycephala) at two water temperatures with single‐dose oral administration

The pharmacokinetics and residue elimination of florfenicol (FFC) and its metabolite florfenicol amine (FFA) were studied in healthy blunt‐snout bream (Megalobrama amblycephala, 50 ± 10 g). The study was conducted with a single‐dose (25 mg/kg) oral administration at a water temperature of 18 or 28°C, while in the residue elimination study, fish were administered at 25 mg/kg daily for three consecutive days by oral gavage to determine the withdrawal period (WDT) at 28°C. The FFC and FFA levels in plasma and tissues (liver, kidneys and muscle) were analysed using high‐performance liquid chromatography (HPLC). A no‐compartment model was used to analyse the concentration versus time data of M. amblycephala. In the two groups at 18 and 28°C, the maximum plasma concentration (C_max) of FFC was 5.89 and 6.21 μg/ml, while the time to reach C_max (T_max) was 5.97 and 2.84 hr, respectively. These suggested that higher temperature absorbed more drug and more quickly at M. amblycephala. And the elimination half‐life (T_1/2kβ) of FFC was calculated as 26.75 and 16.14 hr, while the total body clearance (CL) was 0.09 and 0.15 L kg^?1 hr^?1, and the areas under the concentration–time curves (AUCs) were 265.87 and 163.31 μg hr/ml, respectively. The difference demonstrated that the elimination rate of FFC in M. amblycephala at 28°C was more quickly than that at 18°C. The results of FFA showed the same trend in tissues of M. amblycephala. After multiple oral doses (25 mg/kg daily for 3 days), the k (eliminate rate constant) of FFA in M. amblycephala muscle was 0.017, the C₀ (initial concentration) was 3.07 mg/kg, and the WDT was 10 days (water temperature 28°C).