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1.
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 (T1/2λz), maximum plasma concentration (Cmax), time to peak (Tmax), 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.  相似文献   

2.
To reduce florfenicol (FFC) administration frequency in veterinary use, the drug was currently developed into in situ forming gel. Twelve pigs were randomly divided into two groups (six pigs per group). A single i.m. dose of 40 mg/kg body weight (b.w.) was given to pigs, group one was given FFC in situ forming gel, and group two was given FFC conventional injection. High‐performance liquid chromatography (HPLC) was used to determine FFC plasma concentrations. There were significant differences (P < 0.01) between FFC in situ forming gel and conventional injection, in pharmacokinetic parameters MRT (mean retention time) (57.79 ± 2.88) h versus (15.94 ± 1.29) h, AUC (area under the concentration–time curve) (421.54 ± 8.97) μg·h/mL versus (168.16 ± 4.59) μg·h/mL, tmax (time of occurrence of cmax) (9.00 ± 2.68) h versus (4.33 ± 0.82) h, cmax (maximum plasma concentration) (6.87 ± 0.66) μg/mL versus (12.01 ± 0.66) μg/mL, t1/2λz (terminal elimination half‐life) (38.04 ± 2.20) h versus (9.15 ± 2.71) h. The results demonstrated that the in situ forming gel system could shorten dosing interval of FFC and thus achieved less frequent administration during long‐term treatment.  相似文献   

3.
Three asymptomatic koalas serologically positive for cryptococcosis and two symptomatic koalas were treated with 10 mg/kg fluconazole orally, twice daily for at least 2 weeks. The median plasma Cmax and AUC0‐8 h for asymptomatic animals were 0.9 μg/mL and 4.9 μg/mL·h, respectively; and for symptomatic animals 3.2 μg/mL and 17.3 μg/mL·h, respectively. An additional symptomatic koala was treated with fluconazole (10 mg/kg twice daily) and a subcutaneous amphotericin B infusion twice weekly. After 2 weeks the fluconazole Cmax was 3.7 μg/mL and the AUC0‐8 h was 25.8 μg/mL*h. An additional three koalas were treated with fluconazole 15 mg/kg twice daily for at least 2 weeks, with the same subcutaneous amphotericin protocol co‐administered to two of these koalas (Cmax: 5.0 μg/mL; mean AUC0‐8 h: 18.1 μg/mL*h). For all koalas, the fluconazole plasma Cmax failed to reach the MIC90 (16 μg/mL) to inhibit C. gattii. Fluconazole administered orally at either 10 or 15 mg/kg twice daily in conjunction with amphotericin is unlikely to attain therapeutic plasma concentrations. Suggestions to improve treatment of systemic cryptococcosis include testing pathogen susceptibility to fluconazole, monitoring plasma fluconazole concentrations, and administration of 20–25 mg/kg fluconazole orally, twice daily, with an amphotericin subcutaneous infusion twice weekly.  相似文献   

4.
The pharmacokinetics of doxycycline was studied in plasma after a single dose (20 mg/kg) of intravenous or oral administration to tilapia (Oreochromis aureus × Oreochromis niloticus) reared in fresh water at 24 °C. Plasma samples were collected from six fish per sampling point. Doxycycline concentrations were determined by high‐performance liquid chromatography with a 0.005 μg/mL limit of detection, then were subjected to noncompartmental analysis. Following oral administration, the double‐peak phenomenon was observed, and the first (Cmax1) and second (Cmax2) peaks were 1.99 ± 0.43 μg/mL at 2.0 h and 2.27 ± 0.38 μg/mL at 24.0 h, respectively. After the intravenous injection, a Cmax2 (12.12 ± 1.97 μg/mL) was also observed, and initial concentration of 45.76 μg/mL, apparent elimination rate constant (λz) of 0.018 per h, apparent elimination half‐life (t1/2λz) of 39.0 h, systemic total body clearance (Cl) of 41.28 mL/h/kg, volume of distribution (Vz) of 2323.21 mL/kg, and volume of distribution at steady‐state (Vss) of 1356.69 mL/kg were determined, respectively. While after oral administration, the λz, t1/2λz, and bioavailability of doxycycline were 0.009 per h, 77.2 h, and 23.41%, respectively. It was shown that doxycycline was relatively slowly and incompletely absorbed, extensively distributed, and slowly eliminated in tilapia, in addition, doxycycline might undergo enterohepatic recycling in tilapia.  相似文献   

5.
Bistoletti, M., Alvarez, L., Lanusse, C., Moreno, L. Disposition kinetics of albendazole and metabolites in laying hens. J. vet. Pharmacol. Therap.  36 , 161–168. An increasing prevalence of roundworm parasites in poultry, particularly in litter‐based housing systems, has been reported. However, few anthelmintic drugs are commercially available for use in avian production systems. The anthelmintic efficacy of albendazole (ABZ) in poultry has been demonstrated well. The goal of this work was to characterize the ABZ and metabolites plasma disposition kinetics after treatment with different administration routes in laying hens. Twenty‐four laying hens Plymouth Rock Barrada were distributed into three groups and treated with ABZ as follows: intravenously at 10 mg/kg (ABZ i.v.); orally at the same dose (ABZ oral); and in medicated feed at 10 mg/kg·day for 7 days (ABZ feed). Blood samples were taken up to 48 h posttreatment (ABZ i.v. and ABZ oral) and up to 10 days poststart feed medication (ABZ feed). The collected plasma samples were analyzed using high‐performance liquid chromatography. ABZ and its albendazole sulphoxide (ABZSO) and ABZSO2 metabolites were recovered in plasma after ABZ i.v. administration. ABZ parent compound showed an initial concentration of 16.4 ± 2.0 μg/mL, being rapidly metabolized into the ABZSO and ABZSO2 metabolites. The ABZSO maximum concentration (Cmax) (3.10 ± 0.78 μg/mL) was higher than that of ABZSO2Cmax (0.34 ± 0.05 μg/mL). The area under the concentration vs time curve (AUC) for ABZSO (21.9 ± 3.6 μg·h/mL) was higher than that observed for ABZSO2 and ABZ (7.80 ± 1.02 and 12.0 ± 1.6 μg·h/mL, respectively). The ABZ body clearance (Cl) was 0.88 ± 0.11 L·h/kg with an elimination half‐life (T1/2el) of 3.47 ± 0.73 h. The T1/2el for ABZSO and ABZSO2 were 6.36 ± 1.50 and 5.40 ± 1.90 h, respectively. After ABZ oral administration, low ABZ plasma concentrations were measured between 0.5 and 3 h posttreatment. ABZ was rapidly metabolized to ABZSO (Cmax, 1.71 ± 0.62 μg/mL) and ABZSO2 (Cmax, 0.43 ± 0.04 μg/mL). The metabolite systemic exposure (AUC) values were 18.6 ± 2.0 and 10.6 ± 0.9 μg·h/mL for ABZSO and ABZSO2, respectively. The half‐life values after ABZ oral were similar (5.91 ± 0.60 and 5.57 ± 1.19 h for ABZSO and ABZSO2, respectively) to those obtained after ABZ i.v. administration. ABZ was not recovered from the bloodstream after ABZ feed administration. AUC values of ABZSO and ABZSO2 were 61.9 and 92.4 μg·h/mL, respectively. The work reported here provides useful information on the pharmacokinetic behavior of ABZ after both i.v. and oral administrations in hens, which is a useful first step to evaluate its potential as an anthelmintic tool for use in poultry.  相似文献   

6.
In this study, the pharmacokinetics profiles of difloxacin in the olive flounder (Paralichthys olivaceus) were investigated following intravenous and oral administration (10 mg/kg BW) at 14 and 22 °C water temperatures. Plasma and tissue samples (muscle, liver, and kidney) were analyzed using an HPLC method. The results showed that the plasma concentration–time data for difloxacin were described commendably by two‐compartment open model at the two water temperatures. The absorption half‐life (t1/2ka) of difloxacin after oral administration were 2.08 and 1.10 h at 14 and 22 °C, respectively; whereas the elimination half‐life (t1/2β) was 4.41 and 2.38 h, respectively. The muscle concentration of 1.35 ± 0.19 μg/g was observed at 9 h at 14 °C, and 2.11 ± 0.33 μg/g at 6 h at 22 °C, respectively. For liver, the peak concentration of difloxacin 2.43 ± 0.30 μg/g occurred at 6 h at 14 °C, which was lower than the 3.34 ± 0.24 μg/g peak that occurred at 4 h at 22 °C. The calculated bioavailability of difloxacin was 68.07% at 22 °C, which was higher than the 53.43% calculated for 14 °C. After intravenous administration, the t1/2β were 4.79 and 2.81 h at 14 and 22 °C, respectively. The results indicate that the peak concentrations in muscle and liver at 14 °C are approximately half of those achieved at 22 °C. However, the Cmax in kidney at 14 and 22 °C were similar. The Vd values were 1.20 and 1.75 L/kg at 14 and 22 °C, respectively. These data indicated that both temperature and drug administration had significant effects on the elimination of difloxacin, and lower temperature or oral administration resulted in lower elimination.  相似文献   

7.
Seven sea otters received a single subcutaneous dose of cefovecin at 8 mg/kg body weight. Plasma samples were collected at predetermined time points and assayed for total cefovecin concentrations using ultra‐performance liquid chromatography and tandem mass spectrometry. The mean (±SD) noncompartmental pharmacokinetic indices were as follows: CMax (obs) 70.6 ± 14.6 μg/mL, TMax (obs) 2.9 ± 1.5 h, elimination rate constant (kel) 0.017 ± 0.002/h, elimination half‐life (t1/2kel) 41.6 ± 4.7 h, area under the plasma concentration‐vs.‐time curve to last sample (AUClast) 3438.7 ± 437.7 h·μg/mL and AUC extrapolated to infinity (AUC0→∞) 3447.8 ± 439.0 h·μg/mL. The minimum inhibitory concentrations (MIC) for select isolates were determined and used to suggest possible dosing intervals of 10 days, 5 days, and 2.5 days for gram‐positive, gram‐negative, and Vibrio parahaemolyticus bacterial species, respectively. This study found a single subcutaneous dose of cefovecin sodium in sea otters to be clinically safe and a viable option for long‐acting antimicrobial therapy.  相似文献   

8.
Eighteen Holstein dairy cows ranging in body weight from 500–700 kg and with an average milk yield of 37 ± 6 kg/day were used to investigate the depletion of florfenicol (FFL) in milk and plasma of dairy cows. Three groups of six were administered FFL: Group A, intramammary (IMM) infusion of ~2.5 mg FFL/kg BW at three consecutive milking intervals (total amount of ~7.5 mg/kg BW); Group B, one IMM infusion (20 mg/kg BW) into one quarter and Group C, one subcutaneous (SC) treatment (40 mg/kg BW). IMM infusions were into the right front quarter. Cows were milked daily at 06:00 and 18:00 h. The highest concentrations (Cmax) and time to Cmax (Tmax) were: 1.6 ± 2.2 μg·FFL/mL milk at 22 h (Group A), 5.5 ± 3.6 μg·FFL/mL milk at 12 h (Group B), and 1.7 ± 0.4 μg·FFL/mL milk at 12 h (Group C). The half‐lives (t1/2) were ~19, 5.5, and 60 h, for Groups A, B, and C, respectively. FFL was below the limit of detection (LOD) by 60 h in three Group B cows, but above the LOD at 72, 84, and 120 h in three cows. FFL was above the LOD in milk from Group C's cows for 432–588 h. Plasma values followed the same trends as milk. The results demonstrate that IMM‐infused FFL is bioavailable and below the LOD within 72–120 h. The concentration of FFL was detectable in both plasma and milk over the course of 2–3 weeks after SC administration. The absence of residue depletion data presents problems in determining safe levels of FFL residues in milk and edible tissues. The data presented here must not be construed as approval for extra‐label use in food animals.  相似文献   

9.
The pharmacokinetics and tissue distribution of quinocetone (QCT) in crucian carp (Carassius auratus), common carp (Cyprinus carpio L.), and grass carp (Ctenopharyngodon idella) were compared after oral administration of QCT (50 mg/kg body weight) at water temperature of 24 ± 1 °C. Similar QCT plasma concentration–time profiles were found in the three species of cyprinid fish at the same dosage regimen and water temperature, which were all fitted two‐compartment open pharmacokinetic model. However, different pharmacokinetic parameters were observed in crucian carp, common carp, and grass carp. The absorption rate constants (Ka) of QCT were 1.65, 1.40 and 1.74/h, respectively and absorption half‐lives (t1/2kα) were 0.42, 0.49, and 0.40/h, respectively. The distribution half‐life (t1/2α) was 2.83, 0.67, and 0.88 h, respectively, and elimination half‐lives (t1/2β) of QCT were 133.97, 63.55, and 40.76 h, respectively. The maximum concentrations (Cmax) of QCT in plasma were 0.315, 0.182, and 0.139 μg/mL and the time to peak concentrations (Tp) were 1.45, 0.96, and 1.08 h, respectively. The area under the plasma concentration‐time curves (AUC) were 12.35, 5.99, and 4.52 μg·h/mL, respectively. The distribution volumes (Vd/F) of QCT were calculated as 117.81, 128.71, and 220.10 L/kg, respectively. The tissue analysis showed that a similar regularity was obtained in the three species of cyprinids with a single dose of 50 mg/kg body weight after oral administration at the same water temperature. The tissue concentration of QCT in each fish was in order of liver>kidney>muscle, while the residues of QCT in the three species of cyprinid fish were in order of crucian carp>common carp>grass carp.  相似文献   

10.
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 (Cmax) 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 Cmax (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.  相似文献   

11.
Albarellos, G. A., Montoya, L., Denamiel, G. A. A., Velo, M. C., Landoni, M. F. Pharmacokinetics and bone tissue concentrations of lincomycin following intravenous and intramuscular administrations to cats. J. vet. Pharmacol. Therap.  35 , 534–540. The pharmacokinetic properties and bone concentrations of lincomycin in cats after single intravenous and intramuscular administrations at a dosage rate of 10 mg/kg were investigated. Lincomycin minimum inhibitory concentration (MIC) for some gram‐positive strains isolated from clinical cases was determined. Serum lincomycin disposition was best‐fitted to a bicompartmental and a monocompartmental open models with first‐order elimination after intravenous and intramuscular dosing, respectively. After intravenous administration, distribution was rapid (T1/2(d) = 0.22 ± 0.09 h) and wide as reflected by the volume of distribution (V(d(ss))) of 1.24 ± 0.08 L/kg. Plasma clearance was 0.28 ± 0.09 L/h·kg and elimination half‐life (T1/2) 3.56 ± 0.62 h. Peak serum concentration (Cmax), Tmax, and bioavailability for the intramuscular administration were 7.97 ± 2.31 μg/mL, 0.12 ± 0.05 h, and 82.55 ± 23.64%, respectively. Thirty to 45 min after intravenous administration, lincomycin bone concentrations were 9.31 ± 1.75 μg/mL. At the same time after intramuscular administration, bone concentrations were 3.53 ± 0.28 μg/mL. The corresponding bone/serum ratios were 0.77 ± 0.04 (intravenous) and 0.69 ± 0.18 (intramuscular). Lincomycin MIC for Staphylococcus spp. ranged from 0.25 to 16 μg/mL and for Streptococcus spp. from 0.25 to 8 μg/mL.  相似文献   

12.
The objective of this study was to evaluate the pharmacokinetic characteristics of enrofloxacin (ENR) injectable in situ gel we developed in dogs following a single intramuscular (i.m.) administration. Twelve healthy dogs were randomly divided into two groups (six dogs per group), then administrated a single 20 mg/kg body weight (b.w.) ENR injectable in situ gel and a single 5 mg/kg b.w. ENR conventional injection, respectively. High‐performance liquid chromatography (HPLC) was used to determine ENR plasma concentrations. The pharmacokinetic parameters of ENR injectable in situ gel and conventional injection in dogs are as follows: MRT (mean residence time) (45.59 ± 14.05) h verse (11.40 ± 1.64) h, AUC (area under the blood concentration vs. time curve) (28.66 ± 15.41) μg·h/mL verse (11.06 ± 3.90) μg·h/mL, cmax (maximal concentration) (1.59 ± 0.35) μg/mL verse (1.46 ± 0.07) μg/mL, tmax (time needed to reach cmax) (1.25 ± 1.37) h verse (1.40 ± 0.55) h, t1/2λz (terminal elimination half‐life) (40.27 ± 17.79) h verse (10.32 ± 0.97) h. The results demonstrated that the in situ forming gel system could increase dosing interval of ENR and thus reduced dosing frequency during long‐term treatment. Therefore, the ENR injectable in situ gel seems to be worth popularizing in veterinary clinical application.  相似文献   

13.
A two‐period cross‐over study was carried to investigate the pharmacokinetics (PK) and ex‐vivo pharmacodynamics (PD) of cefquinome when administrated intravenously (IV) and intramuscularly (IM) in seven healthy dogs at a dose of 2 mg/kg of body weight. Serum concentrations were determined by HPLC‐MS/MS assay and cefquinome concentration vs. time data after IV and IM were best fit to a two‐compartment open model. Cefquinome mean values of area under concentration–time curve (AUC) were 5.15 μg·h/mL for IV dose and 4.59 μg·h/mL for IM dose. Distribution half‐lives and elimination half‐lives after IV dose and IM dose were 0.27 and 0.44 h, 1.53 and 1.94 h, respectively. Values of total body clearance (ClB) and volume of distribution at steady‐state (Vss) were 0.49 L·kg/h and 0.81 L/kg, respectively. After IM dose, Cmax was 2.53 μg/mL and the bioavailability was 89.13%. For PD profile, the determined MIC and MBC values against K. pneumonia were 0.030 and 0.060 μg/mL in MHB and 0.032 and 0.064 μg/mL in serum. The ex vivo time‐kill curves also were established in serum. In conjunction with the data on MIC, MBC values and the ex vivo bactericidal activity in serum, the present results allowed prediction that a single cefquinome dosage of 2 mg/kg may be effective in dogs against K. pneumonia infection.  相似文献   

14.
The pharmacokinetics of dantrolene and its active metabolite, 5‐hydroxydantrolene, after a single oral dose of either 5 or 10 mg/kg of dantrolene was determined. The effects of exposure to dantrolene and 5‐hydroxydantrolene on activated whole‐blood gene expression of the cytokines interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) were also investigated. When dantrolene was administered at a 5 mg/kg dose, peak plasma concentration (Cmax) was 0.43 μg/mL, terminal half‐life (t1/2) was 1.26 h, and area under the time–concentration curve (AUC) was 3.87 μg·h/mL. For the 10 mg/kg dose, Cmax was 0.65 μg/mL, t1/2 was 1.21 h, and AUC was 5.94 μg·h/mL. For all calculated parameters, however, there were large standard deviations and wide ranges noted between and within individual dogs: t1/2, for example, ranged from 0.43 to 6.93 h, Cmax ratios ranged from 1.05 to 3.39, and relative bioavailability (rF) values ranged from 0.02 to 1.56. While activated whole‐blood expression of IL‐2 and IFN‐γ as measured by qRT‐PCR was markedly suppressed following exposure to very high concentrations (30 and 50 μg/mL, respectively) of both dantrolene and 5‐hydroxydantrolene, biologically and therapeutically relevant suppression of cytokine expression did not occur at the much lower drug concentrations achieved with oral dantrolene dosing.  相似文献   

15.
The pharmacokinetic characteristics of valnemulin in layer chickens were studied after single intravenous, intramuscular, and oral administration at a dose of 15 mg/kg body weight. Plasma samples at certain time points were collected and the drug concentrations in them by ultra high‐performance liquid chromatography tandem mass spectrometry (UHPLC‐MS). The concentration–time data for each individual were plotted by noncompartmental analysis for the whole three routes. Following intravenous administration, the plasma concentration showed tiny fluctuation. The elimination half‐life (), total body clearance (Cl), and area under the plasma concentration–time curve (AUC) were 1.85 ± 0.43 h, 2.2 ± 0.9 L/h, and 7.52 ± 2.46 μg·h/mL, respectively. Following intramuscular administration, the peak concentration (Cmax, 1.40 ± 0.43 μg/mL) was achieved at the time of 0.34 h. A multiple‐peak phenomenon existed after oral administration, and the first peak and secondary peak were at 10 min and during 2–4 h, respectively, while the tertiary peak appeared during 5–15 h. The bioavailability (F %) for intramuscular and oral administration was 68.60% and 52.64%, respectively. In present study, the detailed pharmacokinetic profiles showed that this drug is widely distributed and rapidly eliminated, however has a low bioavailability, indicating that valnemulin is likely to be a favorable choice in the clinical practice.  相似文献   

16.
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 (Cmax) of FFC was 5.89 and 6.21 μg/ml, while the time to reach Cmax (Tmax) 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 (T1/2kβ) 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).  相似文献   

17.
Lucas, M. F., Errecalde, J. O., Mestorino, N. Pharmacokinetics of azithromycin in lactating dairy cows with subclinical mastitis caused by Staphylococcus aureus. J. vet. Pharmacol. Therap. 33 , 132–140. Azithromycin is a time‐dependent antimicrobial with long persistence. The main characteristics of azithromycin suggest that it could be useful for treating bovine mastitis caused by Staphylococcus aureus. To investigate this possibility, its pharmacokinetic (PK) behavior was studied. Six Holstein lactating cows with subclinical mastitis were administered two 10 mg/kg intramuscular (i.m.) doses of azithromycin, with a 48‐h interval. Milk and plasma concentrations were measured by microbiological assay. The MIC90 was determined in 51 S. aureus isolations to calculate pharmacokinetic/pharmacodynamic (PK/PD) parameters. Milk maximal concentration (Cmax) was 7.76 ± 1.76 μg/mL (16.67 h post‐first administration) and 7.82 ± 2.18 μg/mL (14 h post‐2nd administration). In plasma Cmax was 0.18 ± 0.03 μg/mL (2 h post‐1rst administration) and 0.11 ± 0.03 μg/mL (14 h post‐2nd administration). Azithromycin was eliminated from the milk with a half‐life (T½λ) of 158.26 ± 137.7 h after 2nd administration, meanwhile plasma T½λ resulted shorter(13.97 ± 11.1 h). The mean area under the concentration vs. time curve from 0 to 24 h (AUC0‐24h) was 153.82 ± 34.66 μg·h/mL in milk secretion and 2.61 ± 0.59 μg·h/mL in plasma. Infection presence in the quarters had a significant effect (P < 0.05) on the area under the concentration vs. time curve from 0 to infinity (AUC0‐∞) and clearance from the mammary gland (Clmam/F). Moreover, it had influence on milk bioavailability (Fmilk), T½λ, AUC0‐∞ and mean residence time (MRT) in milk, which values resulted increased in mastitic quarters. In this study, it was determined that the production level and the mammary health status have an influence on PK parameters of azithromycin treatments in bovine mastitis.  相似文献   

18.
The pharmacokinetics of florfenicol (FF) and its metabolite, florfenicol amine (FFA), were studied in rice field eel (Monopterus albus) after a single dose (20 mg/kg) by intramuscular (i.m.) or oral gavage (p.o.) dose at 25 °C. The elimination half‐lives (t1/2β), peak concentration of FF (Cmax), and time to reach FF peak concentration (Tmax) in plasma were estimated as 18.39 h, 10.83 μg/mL, and 7.00 h, respectively, after i.m. injection and 13.46 h, 8.37 μg/mL, and 5 h, respectively, after p.o. administration. The Tmax values of FF in tissues (i.e., kidney, muscle, and liver) were larger for i.m. injection compared with those for p.o. administration. The t1/2β had the following order kidney > muscle > liver for i.m. administrated and kidney > liver > muscle for p.o. administrated. The largest area under the concentration–time curve (AUC) was calculated to be 384.29 mg · h/kg after i.m. dosing, and the mean residence time (MRT) was 42.46 h by oral administration in kidney. FFA was also found in all tissues with a lower concentration than FF for both i.m. and p.o. administrations throughout the study. The elimination of FFA was slow with a t1/2β between 18.19 and 47.80 h in plasma and tissues. The mean metabolic rate of FFA for i.m. and p.o. administrations was >23.30%.  相似文献   

19.
Dechant, J. E., Rowe, J. D., Byrne, B. A., Wetzlich, S. E., Kieu, H. T., Tell, L. A. Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos). J. vet. Pharmacol. Therap.  36 , 122–129. Six adult male alpacas received one subcutaneous administration of ceftiofur crystalline free acid (CCFA) at a dosage of 6.6 mg/kg. After a washout period, the same alpacas received three subcutaneous doses of 6.6 mg/kg CCFA at 5‐day intervals. Blood samples collected from the jugular vein before and at multiple time points after each CCFA administration were assayed for ceftiofur‐ and desfuroylceftiofur‐related metabolite concentrations using high‐performance liquid chromatography. Pharmacokinetic disposition of CCFA was analyzed by a noncompartmental approach. Mean pharmacokinetic parameters (±SD) following single‐dose administration of CCFA were Cmax (2.7 ± 0.9 μg/mL); Tmax (36 ± 0 h); area under the curve AUC0→∞ (199.2 ± 42.1 μg·h/mL); terminal phase rate constant λz (0.02 ± 0.003/h); and terminal phase rate constant half‐life t1/2λz (44.7 h; harmonic). Mean terminal pharmacokinetic parameters (±SD) following three administrations of CCFA were Cmax (2.0 ± 0.4 μg/mL); Tmax (17.3 ± 16.3 h); AUC0→∞ (216.8 ± 84.5 μg·h/mL); λz (0.01 ± 0.003/h); and t1/2λz (65.9 h; harmonic). The terminal phase rate constant and the Tmax were significantly different between single and multiple administrations. Local reactions were noted in two alpacas following multiple CCFA administrations.  相似文献   

20.
Experiments in different animal species have shown that febrile conditions, induced by Escherichia coli lipopolysaccharide (LPS), may alter the pharmacokinetic properties of drugs. The objective was to study the effects of a LPS‐induced acute‐phase response (APR) model on plasma pharmacokinetics of florfenicol (FFC) after its intravenous administration in sheep. Six adult clinically healthy Suffolk Down sheep, 8 months old and 35.5 ± 2.2 kg in body weight (bw), were distributed through a crossover factorial 2 × 2 design, with 4 weeks of washout. Pairs of sheep similar in body weight were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 μg/kg bw of E. coli LPS before FFC treatment. Group 2 (control) was treated with an equivalent volume of saline solution (SS) at similar intervals as LPS. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples (5 mL) were collected before drug administration and at different times between 0.05 and 48.0 h after treatment. FFC plasma concentrations were determined by liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using a Mann–Whitney U‐test. The mean values of AUC0–∞ in the endotoxaemic sheep (105.9 ± 14.3 μg·h/mL) were significantly higher (P < 0.05) than values observed in healthy sheep (78.4 ± 5.2 μg·h/mL). The total mean plasma clearance (CLT) decreased from 257.7 ± 16.9 mL·h/kg in the control group to 198.2 ± 24.1 mL·h/kg in LPS‐treated sheep. A significant increase (P < 0.05) in the terminal half‐life was observed in the endotoxaemic sheep (16.9 ± 3.8 h) compared to the values observed in healthy sheep (10.4 ± 3.2 h). In conclusion, the APR induced by the intravenous administration of E. coli LPS in sheep produces higher plasma concentrations of FFC due to a decrease in the total body clearance of the drug.  相似文献   

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