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1.
For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been considered as the gold standard for estimating the antibacterial efficacy. In this study, the pharmacokinetics of florfenicol (FF) in porcine lung interstitial fluid was investigated after single intramuscular administration at two different doses (20 and 50 mg/kg). Twelve pigs underwent thoracotomy under general anesthesia. Then, the CMA/30 probe was implanted into the lung and perfused at 1 μL/min. The microdialysis (MD) samples were collected on a preset schedule and analyzed by high‐performance liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis was performed. FF exhibited rapid distribution and slow elimination in porcine lung interstitial fluid. The main pharmacokinetic parameters at 20 and 50 mg/kg were 4.88 ± 0.54 and 10.36 ± 2.52 μg/mL for the maximum concentration (Cmax), 3.25 ± 0.32 and 3.50 ± 0.27 h for the time to Cmax (Tmax), 9.47 ± 6.84 and 7.75 ± 3.23 h for the half‐life (t1/2), 0.10 ± 0.06 and 0.10 ± 0.04 1/h for the terminal elimination rate constant (λz), 13.85 ± 7.97 and 11.42 ± 2.79 h for the mean residence time (MRT), 37.77 ± 8.13 and 71.15 ± 16.99 h·μg/mL for the area under the curve from time 0 to 18.25 h (AUC0–18.25), and 51.18 ± 20.11 and 88.78 ± 27.58 h·μg/mL for the area under the curve from time 0 to infinity (AUC0–∞), respectively.  相似文献   

2.
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   

3.
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 Cmax was 6.30 μg/mL, and the AUCINF 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.  相似文献   

4.
Huang, R. A., Letendre, L. T., Banav, N., Fischer, J., Somerville, B. Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity. J. vet. Pharmacol. Therap. 33 , 227–237. The pharmacokinetics (PK) and dose proportionality of gamithromycin (ZACTRAN®), a novel azalide, after a single intravenous (i.v.) dose of 3 mg/kg or subcutaneous (s.c.) injection at 3, 6 and 9 mg/kg body weight were studied in 13 male castrate and 13 female Angus cattle. Following i.v. administration, the mean area under the curve extrapolated to infinity (AUCinf) was 4.28 ± 0.536 μg·h/mL, and mean elimination half‐life (t1/2) was 44.9 ± 4.67 h, with a large volume of distribution (Vss) of 24.9 ± 2.99 L/kg and a high clearance rate (Clobs) of 712 ± 95.7 mL/h/kg. For cattle treated with s.c. injection of 3, 6 or 9 mg/kg, mean AUCinf values were 4.55 ± 0.690, 9.42 ± 1.11 and 12.2 ± 1.13 μg·h/mL, respectively, and the mean elimination half‐lives (t1/2) were 51.2 ± 6.10, 50.8 ± 3.80 and 58.5 ± 5.50 h. Gamithromycin was well absorbed and fully bioavailable (97.6–112%) after s.c. administration. No statistically significant (α = 0.05) gender differences in the AUCInf or elimination half‐life values were observed. Dose proportionality was established based on AUCInf over the range of 0.5 to 1.5 times of the recommended dosage of 6 mg/kg of body weight. Further investigations were conducted to assess plasma PK, lung/plasma concentration ratios and plasma antibacterial activity using 36 cattle. The average maximum gamithromycin concentration measured in whole lung homogenate was 18 500 ng/g at first sampling time of 1 day (～24 h) after treatment. The ratios of lung to plasma concentration were 265, 410, 329 and 247 at 1, 5, 10 and 15 days postdose. The lung AUCinf was 194 times higher than the corresponding plasma AUCinf. The apparent elimination half‐life for gamithromycin in lung was 90.4 h (～4 days). Antibacterial activity was observed with plasma collected at 6 h postdose with a corresponding average gamithromycin plasma concentration of 261 ng/mL. In vitro plasma protein binding in bovine plasma was determined to be 26.0 ± 0.60% bound over a range of 0.1–3.0 μg/mL of gamithromycin. The dose proportionality of AUC, high bioavailability, rapid and extensive distribution to lung tissue and low level of plasma protein binding are beneficial PK parameters for an antimicrobial drug used for the treatment and prevention of bovine respiratory disease.  相似文献   

5.
Eight adult female dairy goats received one subcutaneous administration of tulathromycin at a dosage of 2.5 mg/kg body weight. Blood and milk samples were assayed for tulathromycin and the common fragment of tulathromycin, respectively, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of tulathromycin was analyzed by a noncompartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single‐dose administration of tulathromycin were as follows: Cmax (121.54 ± 19.01 ng/mL); Tmax (12 ± 12–24 h); area under the curve AUC0→∞ (8324.54 ± 1706.56 ng·h/mL); terminal‐phase rate constant λz (0.01 ± 0.002 h−1); and terminal‐phase rate constant half‐life t1/2λz (67.20 h; harmonic). Mean milk pharmacokinetic parameters (±SD) following 45 days of sampling were as follows: Cmax (1594 ± 379.23 ng/mL); Tmax (12 ± 12–36 h); AUC0→∞ (72,250.51 ± 18,909.57 ng·h/mL); λz (0.005 ± 0.001 h−1); and t1/2λz (155.28 h; harmonic). All goats had injection‐site reactions that diminished in size over time. The conclusions from this study were that tulathromycin residues are detectable in milk samples from adult goats for at least 45 days following subcutaneous administration, this therapeutic option should be reserved for cases where other treatment options have failed, and goat milk should be withheld from the human food chain for at least 45 days following tulathromycin administration.  相似文献   

6.
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 (Cmax) in healthy pigs was 586 ± 71 ng/mL, reached by 0.5 h, while the mean value for Cmax 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 t1/2el = 126 h in plasma and t1/2el = 165 h in lung, as well as longer drug persistent in infected pigs, was found.  相似文献   

7.
The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α‐hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one‐compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single‐dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0–∞) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1–12 h). Alpha‐hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.  相似文献   

8.
The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra‐articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3‐way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half‐life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (Cmax) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0–2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on Cmax:MIC of 10.  相似文献   

9.
Intravenous benzodiazepines are utilized as first‐line drugs to treat prolonged epileptic seizures in dogs and alternative routes of administration are required when venous access is limited. This study compared the pharmacokinetics of midazolam after intravenous (IV), intramuscular (IM), and rectal (PR) administration. Six healthy dogs were administered 0.2 mg/kg midazolam IV, IM, or PR in a randomized, 3‐way crossover design with a 3‐day washout between study periods. Blood samples were collected at baseline and at predetermined intervals until 480 min after administration. Plasma midazolam concentrations were measured by high‐pressure liquid chromatography with UV detection. Rectal administration resulted in erratic systemic availability with undetectable to low plasma concentrations. Arithmetic mean values ± SD for midazolam peak plasma concentrations were 0.86 ± 0.36 μg/mL (C0) and 0.20 ± 0.06 μg/mL (Cmax), following IV and IM administration, respectively. Time to peak concentration (Tmax) after IM administration was 7.8 ± 2.4 min with a bioavailability of 50 ± 16%. Findings suggest that IM midazolam might be useful in treating seizures in dogs when venous access is unavailable, but higher doses may be needed to account for intermediate bioavailability. Rectal administration is likely of limited efficacy for treating seizures in dogs.  相似文献   

10.
Ribavirin is an antiviral used in human medicine, but it has not been authorized for use in veterinary medicine although it is effective against infectious salmon anemia (ISA) virus, between others. In this study, we present a pharmacokinetic profile of ribavirin in Atlantic salmon (Salmo salar), efficacy prediction indexes, and the measure of its withdrawal time. To determine the pharmacokinetic profile, fishes were orally administered with a single ribavirin dose of 1.6 mg/kg bw, and then, plasma concentrations were measured at different times. From the time‐vs.‐concentration curve, Cmax = 413.57 ng/mL, Tmax = 6.96 h, AUC = 21394.01 μg·h/mL, t1/2 = 81.61 h, and K10 = 0.0421/h were obtained. Ribavirin reached adequate concentrations during the pharmacokinetic study, with prediction indexes of Cmax/IC50 = 20.7, AUC/IC50 = 1069.7, and T>IC50 = 71 h, where IC is the inhibitory concentration 50%. For ribavirin depletion study, fishes were orally administered with a dairy dose of 1.6 mg/kg bw during 10 days. Concentrations were measured on edible tissue on different days post‐treatment. A linear regression of the time vs. concentration was conducted, obtaining a withdrawal time of 1966 °C days. Results obtained reveal that the dose of 1.6 mg/kg bw orally administered is effective for ISA virus, originating a reasonable withdrawal period within the productive schedules of Atlantic salmon.  相似文献   

11.
The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty‐four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR‐IV (10 mg/kg, IV), ENR‐IM (10 mg/kg, IM), DNX‐IV (8 mg/kg, IV), and DNX‐IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high‐pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half‐life (t1/2λz) 11.16 and 17.47 hr, area under the plasma concentration–time curve (AUC0‐48) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady‐state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr?1 kg?1, respectively. The PK parameters of ENR and DNX following IM injection were t1/2λz 21.10 and 28.41 hr, AUC0‐48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC0‐48CPR/AUC0‐48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC0‐24/minimum inhibitory concentration (MIC) and maximum concentration (Cmax)/MIC ratios for susceptible bacteria, with the MIC90 of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.  相似文献   

12.
The aims of this study were to establish optimal doses of doxycycline (dox) against Haemophilus parasuis on the basis of pharmacokinetic–pharmacodynamic (PK‐PD) integration modeling. The infected model was established by intranasal inoculation of organism in pigs and confirmed by clinical signs, blood biochemistry, and microscopic examinations. The recommended dose (20 mg/kg b.w.) was administered in pigs through intramuscular routes for PK studies. The area under the concentration 0‐ to 24‐hr curve (AUC0–24), elimination half‐life (T½ke), and mean residence time (MRT) of dox in healthy and H. parasuis‐infected pigs were 55.51 ± 5.72 versus 57.10 ± 4.89 μg·hr/ml, 8.28 ± 0.91 versus 9.80 ± 2.38 hr, and 8.43 ± 0.27 versus 8.79 ± 0.18 hr, respectively. The minimal inhibitory concentration (MIC) of dox against 40 H. parasuis isolates was conducted through broth microdilution method, the corresponding MIC50 and MIC90 were 0.25 and 1 μg/ml, respectively. The Ex vivo growth inhibition data suggested that dox exhibited a concentration‐dependent killing mechanism. Based on the observed AUC24 hr/MIC values by modeling PK‐PD data in H. parasuis‐infected pigs, the doses predicted to obtain bacteriostatic, bactericidal, and elimination effects for H. parasuis over 24 hr were 5.25, 8.55, and 10.37 mg/kg for the 50% target attainment rate (TAR), and 7.26, 13.82, and 18.17 mg/kg for 90% TAR, respectively. This study provided a more optimized alternative for clinical use and demonstrated that the dosage 20 mg/kg of dox by intramuscular administration could have an effective bactericidal activity against H. parasuis.  相似文献   

13.
Tulathromycin is approved for the treatment of respiratory disease in cattle and swine. It is intended for long‐acting, single‐dose injection therapy (Draxxin), making it particularly desirable for use in bison due to the difficulty in handling and ease of creating stress in these animals. The pharmacokinetic properties of tulathromycin in bison were investigated. Ten wood bison received a single 2.5 mg/kg subcutaneous injection of Draxxin. Serum concentrations were measured by liquid chromatography–mass spectrometry (LC‐MS) detection. Tulathromycin demonstrated early maximal serum concentrations, extensive distribution, and slow elimination characteristics. The mean maximum serum concentration (Cmax) was 195 ng/mL at 1.04 h (tmax) postinjection. The mean area under the serum concentration–time curve, extrapolated to infinity (AUC0–inf), was 9341 ng·h/mL. The mean apparent volume of distribution (Vd/F) and clearance (Cls/F) was 111 L/kg and 0.4 L/h/kg, respectively, and the mean half‐life (t1/2) was 214 h (8.9 days). Compared to values for cattle, Cmax and AUC0–inf were lower in bison, while the Vd/F was larger and the t1/2 longer. Tissue distribution and clinical efficacy studies in bison are needed to confirm the purported extensive distribution of tulathromycin into lung tissue and to determine whether a 2.5 mg/kg subcutaneous dosage is adequate for bison.  相似文献   

14.
The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin (MBF) were determined in six healthy female goats of age 1.00–1.25 years after repeated administration of MBF. The MBF was administered intramuscularly (IM) at 2 mg kg?1 day?1 for 5 days. Plasma concentrations of MBF were determined by high‐performance liquid chromatography, and PK parameters were obtained using noncompartmental analysis. The MBF concentrations peaked at 1 hr, and peak concentration (Cmax) was 1.760 µg/ml on day 1 and 1.817 µg/ml on day 5. Repeated dosing of MBF caused no significant change in PK parameters except area under curve (AUC) between day 1 (AUC0–∞D1 = 7.67 ± 0.719 µg × hr/ml) and day 5 (AUC0‐∞D5 = 8.70 ± 0.857 µg × hr/ml). A slight difference in mean residence time between 1st and 5th day of administration and accumulation index (AI = 1.13 ± 0.017) suggested lack of drug accumulation following repeated IM administration up to 5 days. Minimum inhibitory concentration (MIC) demonstrated that Escherichia coli (MIC = 0.04 µg/ml) and Pasturella multocida (MIC = 0.05 µg/ml) were highly sensitive to MBF. Time‐kill kinetics demonstrated rapid and concentration‐dependent activity of MBF against these pathogens. PK/PD integration of data for E. coli and P. multocida, using efficacy indices: Cmax/MIC and AUC0–24hr/MIC, suggested that IM administration of MBF at a dose of 2 mg kg?1 day?1 is appropriate to treat infections caused by E. coli. However, a dose of 5 mg kg?1 day?1 is recommended to treat pneumonia caused by P. multocida in goats. The study indicated that MBF can be used repeatedly at dosage of 2 mg/kg in goats without risk of drug accumulation up to 5 days.  相似文献   

15.
Sellers, G., Lin, H. C., G. Riddell, M. G., Ravis, W. R., Lin, Y. J., Duran, S. H., Givens, M.D. Pharmacokinetics of ketamine in plasma and milk of mature Holstein cows. J. vet. Pharmacol. Therap. 33 , 480–484. The purpose of this study was to evaluate the pharmacokinetics of ketamine in mature Holstein cows following administration of a single intravenous (i.v.) dose. Plasma and milk concentrations were determined using a high‐performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following i.v. administration, plasma Tmax was 0.083 h and plasma Cmax was 18 135 ± 22 720 ng/mL. Plasma AUC was 4484 ± 1,398 ng·h/mL. Plasma t½β was 1.80 ± 0.50 h and mean residence time was 0.794 ± 0.318 h with total body clearance of 1.29 ± 0.70 L/h/kg. The mean plasma steady‐state volume of distribution was calculated as 0.990 ± 0.530 L/kg and volume of distribution based on area was calculated as 3.23 ± 1.51 L/kg. The last measurable time for ketamine detection in plasma was 8.0 h with a mean concentration of 24.9 ± 11.8 ng/mL. Milk Tmax was detected at 0.67 ± 0.26 h with Cmax of 2495 ± 904 ng/mL. Milk AUC till the last time was 6593 ± 2617 ng·h/mL with mean AUC milk to AUC plasma ratio of 1.99 ± 2.15. The last measurable time that ketamine was detected in milk was 44 ± 10.0 h with a mean concentration of 16.0 ± 9.0 ng/mL.  相似文献   

16.
Ketorolac (KET) is a nonsteroidal anti‐inflammatory drug approved for the use in humans that possesses a potent analgesic activity, comparable to morphine, and could represent a useful tool to control acute pain also in animals. The clinical efficacy and pharmacokinetic profile of intravenous (IV) ketorolac tromethamine (0.5 mg/kg) were studied in 15 dogs undergoing gonadectomy. Intra‐operative cardiorespiratory variables were monitored, and post‐operative pain was assessed using a subjective pain score (0–24) in all dogs, whereas the pharmacokinetic profile of the drug was determined in 10 animals. During surgery, mean minimal alveolar concentration of isoflurane was 1.69 ± 0.11%, and normocapnia and spontaneous ventilation were maintained in all animals. During pain assessment, no significant differences between males and females were found, and in no case rescue analgesia was necessary. No adverse effects were reported. Serum samples were purified by solid‐phase extraction and analysed by HPLC with UV‐Vis detection. A large variability was observed in serum concentrations. The kinetics of ketorolac was described by a noncompartmental analysis. The elimination half‐life (t½λz) and ClB were 10.95 ± 7.06 h and 92.66 ± 84.49 mL/h/kg, respectively, and Vdss and Vz were 1030.09 ± 620.50 mL/kg and 1512.25 ± 799.13 mL/kg, respectively. AUC(0→last) and MRT(0→last) were 6.08 ± 3.28 h × μg/mL and 5.59 ± 2.12 h, respectively. The results indicate that ketorolac possess good post‐operative analgesic effects until about 6 h after administration in dogs undergoing moderately painful surgery.  相似文献   

17.
The disposition of plasma glycopyrrolate (GLY) is characterized by a three‐compartment pharmacokinetic model after a 1‐mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V1), volume of distribution at steady‐state (Vss), and area under the plasma concentration–time curve (AUC0‐inf) were 16.7 (13.6–21.7) mL/min/kg, 0.167 (0.103–0.215) L/kg, 3.69 (0.640–38.73) L/kg, and 2.58 (2.28–2.88) ng*h/mL, respectively. Renal clearance of GLY was characterized by a median (range) of 2.65 (1.92–3.59) mL/min/kg and represented approximately 11.3–24.7% of the total plasma clearance. As a result of these studies, we conclude that the majority of GLY is cleared through hepatic mechanisms because of the limited extent of renal clearance of GLY and absence of plasma esterase activity on GLY metabolism. Although the disposition of GLY after intravenous administration to Standardbred horses was similar to that in Thoroughbred horses, differences in some pharmacokinetic parameter estimates were evident. Such differences could be attributed to breed differences or study conditions. The research could provide valuable data to support regulatory guidelines for GLY in Standardbred horses.  相似文献   

18.
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   

19.
The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client‐owned dogs received a CRI of CA at a dose of 25 mg/m2/h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high‐pressure liquid chromatography. The mean peak concentration (CMAX) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1‐ and 8‐h time points. The steady‐state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma.  相似文献   

20.
The objective of this study was to determine the pharmacokinetics of single‐ and multi‐dose ceftiofur crystalline‐free acid (CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1–3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48‐h intervals. Blood samples were collected at pre‐determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured using high‐performance liquid chromatography. Following single‐dose administration of CCFA, the mean ± standard deviation maximum observed plasma concentration was 3.1 ± 0.6 μg/mL and observed time to maximal plasma concentration was 14.0 ± 4.9 h. Following multi‐dose administration of CCFA, the mean ±standard deviation times above CFAE concentrations of ≥0.5 μg/mL and ≥2.0 μg/mL were 192.95 ± 15.86 h and 78.80 ± 15.31 h, respectively. The mean ± standard deviation area under the concentration vs time curve (AUC0→∝) was 246.2 ± 30.7 h × μg/mL and 172.7 ± 27.14 h × μg/mL following single‐ and multi‐dose CCFA administrations, respectively. Subcutaneous administration of CCFA at 13.2 mg/kg in neonatal foals was clinically well‐ tolerated and resulted in plasma concentrations sufficient for the treatment of most bacterial pathogens associated with neonatal foal septicemia. Multi‐dose administration of four doses at dosing interval of 48 h between treatments maintains appropriate therapeutic concentrations in neonatal foals.  相似文献   

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