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1.
Cefuroxime pharmacokinetic profile was investigated in 6 Beagle dogs after single intravenous, intramuscular, and subcutaneous administration at a dosage of 20 mg/kg. Blood samples were withdrawn at predetermined times over a 12‐h period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. Peak plasma concentration (Cmax), time‐to‐peak plasma concentration (Tmax), and bioavailability for the intramuscular and subcutaneous administration were (mean ± SD) 22.99 ± 7.87 μg/mL, 0.43 ± 0.20 h, and 79.70 ± 14.43% and 15.37 ± 3.07 μg/mL, 0.99 ± 0.10 h, and 77.22 ± 21.41%, respectively. Elimination half‐lives and mean residence time for the intravenous, intramuscular, and subcutaneous administration were 1.12 ± 0.19 h and 1.49 ± 0.21 h; 1.13 ± 0.13 and 1.79 ± 0.24 h; and 1.04 ± 0.23 h and 2.21 ± 0.23 h, respectively. Significant differences were found between routes for Ka, MAT, Cmax, Tmax, t½(a), and MRT. T > MIC = 50%, considering a MIC of 1 μg/mL, was 11 h for intravenous and intramuscular administration and 12 h for the subcutaneous route. When a MIC of 4 μg/mL is considered, T > MIC = 50% for intramuscular and subcutaneous administration was estimated in 8 h.  相似文献   

2.
The disposition of spiramycin and lincomycin was measured after intravenous (i.v.) and oral (p.o.) administration to pigs. Twelve healthy pigs (six for each compound) weighing 16–43 kg received a dose of 10 mg/kg intravenously, and 55 mg/kg (spiramycin) or 33 mg/kg (lincomycin) orally in both a fasted and a fed condition in a three-way cross-over design. Spiramycin was detectable in plasma up to 30 h after intravenous and oral administration to both fasted and fed pigs, whereas lincomycin was detected for only 12 h after intravenous administration and up to 15 h after oral administration. The volume of distribution was 5.6 ± 1.5 and 1.1 ± 0.2 L/kg body weight for spiramycin and lincomycin, respectively. For both compounds the bioavailability was strongly dependent on the presence of food in the gastrointestinal tract. For spiramycin the bioavailability was determined to be 60% and 24% in fasted and fed pigs, respectively, whereas the corresponding figures for lincomycin were 73% and 41%. The maximum plasma concentration of spiramycin (Cmax) was estimated to be 5 μg/mL in fasted pigs and 1 μg/mL only in fed pigs. It is concluded that an oral dose of 55 mg/kg body weight is not enough to give a therapeutically effective plasma concentration of spiramycin against species of Mycoplasma, Streptoccocus, Staphylococcus and Pasteurella multocida. The maximum plasma concentration of lincomycin was estimated to be 8 μg/mL in fasted pigs and 5 μg/mL in fed pigs, but as the minimum inhibitory concentration for lincomycin against Actinobacillus pleuropneumoniae and P. multocida is higher than 32 μg/mL a therapeutically effective plasma concentration could not be obtained following oral administration of the drug. For Mycoplasma the MIC90 is below 1 μg/mL and a therapeutically effective plasma concentration of lincomycin was thus obtained after oral administration to both fed and fasted pigs.  相似文献   

3.
The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two‐phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48‐h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two‐compartment open model after i.v. dosing. The half‐lives of distribution and elimination were 0.21 ± 0.13 and 2.58 ± 0.51 h, respectively. The volume of distribution at steady‐state was 0.81 ± 0.26 L/kg, the total body clearance (Cltot) was 0.21 ± 0.18 L/h/kg, and the areas under the concentration–time curves (AUCs) were 18.79 ± 4.57 μg.h/mL. Following i.m. administration, the mean t1/2el and AUC values were 2.94 ± 0.78 h and 17.21 ± 4.36 μg.h/mL. The bioavailability was high (91.76% ± 12.68%), with a peak plasma mean concentration (Cmax) of 2.85 ± 0.89 μg/mL attained at 1.56 ± 0.71 h (Tmax). The in vitro protein binding percentage was 27.84%. Calculation of efficacy predictors showed that levofloxacin might have a good therapeutic profile against Gram‐negative and Gram‐positive bacteria, with an MIC ≤ 0.1 μg/mL.  相似文献   

4.
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   

5.
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   

6.
Holmes, K., Bedenice, D., Papich, M. G. Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection. J. vet. Pharmacol. Therap.  35 , 382–388. A single dose of florfenicol (Nuflor®) was administered to eight healthy adult alpacas at 20 mg/kg intramuscular (i.m.) and 40 mg/kg subcutaneous (s.c.) using a randomized, cross‐over design, and 28‐day washout period. Subsequently, 40 mg/kg florfenicol was injected s.c. every other day for 10 doses to evaluate long‐term effects. Maximum plasma florfenicol concentrations (Cmax, measured via high‐performance liquid chromatography) were achieved rapidly, leading to a higher Cmax of 4.31 ± 3.03 μg/mL following administration of 20 mg/kg i.m. than 40 mg/kg s.c. (Cmax: 1.95 ± 0.94 μg/mL). Multiple s.c. dosing at 48 h intervals achieved a Cmax of 4.48 ± 1.28 μg/mL at steady state. The area under the curve and terminal elimination half‐lives were 51.83 ± 11.72 μg/mL·h and 17.59 ± 11.69 h after single 20 mg/kg i.m. dose, as well as 99.78 ± 23.58 μg/mL·h and 99.67 ± 59.89 h following 40 mg/kg injection of florfenicol s.c., respectively. Florfenicol decreased the following hematological parameters after repeated administration between weeks 0 and 3: total protein (6.38 vs. 5.61 g/dL, P < 0.0001), globulin (2.76 vs. 2.16 g/dL, P < 0.0003), albumin (3.61 vs. 3.48 g/dL, P = 0.0038), white blood cell count (11.89 vs. 9.66 × 103/μL, P < 0.044), and hematocrit (27.25 vs. 24.88%, P < 0.0349). Significant clinical illness was observed in one alpaca. The lowest effective dose of florfenicol should thus be used in alpacas and limited to treatment of highly susceptible pathogens.  相似文献   

7.
Wang, R., Yuan, L.G., He, L.M., Zhu, L.X., Luo, X.Y., Zhang, C.Y., Yu, J.J., Fang, B.H., Liu, Y.H. Pharmacokinetics and bioavailability of valnemulin in broiler chickens. J. vet. Pharmacol. Therap. 34 , 247–251. The objective of this study was to investigate the pharmacokinetics and bioavailability of valnemulin in broiler chickens after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 10 mg/kg body weight (bw). Plasma samples were analyzed by high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS). Pharmacokinetic characterization was performed by non‐compartmental analysis using WinNonlin program. After intravenous administration, distribution was wide with the volume of distribution based on terminal phase(Vz) of 4.27 ± 0.99 L /kg. Mean valnemulin t1/2β(h), Clβ(L /h /kg), Vss (L /kg) and AUC(0–∞)(μg·h /mL) values were 2.85, 0.99, 2.72 and 10.34, respectively. After intramuscular administration, valnemulin was rapidly absorbed with a Cmax of 2.2 μg/mL achieved at 0.43 h (tmax), and the absolute bioavailability (F) was 88.81%; and for the oral route the same parameters were 0.66 ± 0.15 μg/mL, 1.54 ± 0.27 h and 74.42%. A multiple‐peak phenomenon was present after oral administration. The plasma profile of valnemulin exhibited a secondary peak during 2–6 h and a tertiary peak at 32 h. The favorable PK behavior, such as the wide distribution, slow elimination and acceptable bioavailability indicated that it is likely to be effective in chickens.  相似文献   

8.
Javsicas, LH., Giguère, S., Womble, AY. Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide‐susceptible and macrolide‐resistant Rhodococcus equi isolates. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01151.x. The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide‐susceptible and macrolide‐resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6–10‐week‐old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was used to determine the MIC of telithromycin, azithromycin, clarithromycin and erythromycin against R. equi. Following intragastric administration, mean ± SD time to peak serum telithromycin activity (Tmax) was 1.75 ± 0.76 h, maximum serum activity (Cmax) was 1.43 ± 0.37 μg/mL, and terminal half‐life (t½) was 3.81 ± 0.40 h. Telithromycin activity, 4 h postadministration was significantly higher in BAL cells (50.9 ± 14.5 μg/mL) than in PELF (5.07 ± 2.64 μg/mL), and plasma (0.84 ± 0.25 μg/mL). The MIC90 of telithromycin for macrolide‐resistant R. equi isolates (8 μg/mL) was significantly higher than that of macrolide‐susceptible isolates (0.25 μg/mL). The MIC of telithromycin for macrolide‐resistant isolates (MIC50 = 4.0 μg/mL) was significantly lower than that of clarithromycin (MIC50 = 24.0 μg/mL), azithromycin (MIC50 =256 μg/mL) and erythromycin (MIC50 = 24 μg/mL).  相似文献   

9.
The pharmacokinetics and bioavailability of butafosfan in piglets were investigated following intravenous and intramuscular administration at a single dose of 10 mg/kg body weight. Plasma concentration–time data and relevant parameters were best described by noncompartmental analysis after intravenous and intramuscular injection. The data were analyzed through WinNolin 6.3 software. After intravenous administration, the mean pharmacokinetic parameters were determined as T1/2λz of 3.30 h, Cl of 0.16 L kg/h, AUC of 64.49 ± 15.07 μg h/mL, Vss of 0.81 ± 0.44/kg, and MRT of 1.51 ± 0.27 h. Following intramuscular administration, the Cmax (28.11 μg/mL) was achieved at Tmax (0.31 h) with an absolute availability of 74.69%. Other major parameters including AUC and MRT were 48.29 ± 21.67 μg h/mL and 1.74 ± 0.29 h, respectively.  相似文献   

10.
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   

11.
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   

12.
Malreddy, P. R., Coetzee, J. F., KuKanich, B., Gehring, R. Pharmacokinetics and milk secretion of gabapentin and meloxicam co‐administered orally in Holstein‐Friesian cows. J. vet. Pharmacol. Therap.  36 , 14–20. Management of neuropathic pain in dairy cattle could be achieved by combination therapy of gabapentin, a GABA analog and meloxicam, an nonsteroidal anti‐inflammatory drug. This study was designed to determine specifically the depletion of these drugs into milk. Six animals received meloxicam at 1 mg/kg and gabapentin at 10 mg/kg, while another group (n = 6) received meloxicam at 1 mg/kg and gabapentin at 20 mg/kg. Plasma and milk drug concentrations were determined over 7 days postadministration by HPLC/MS followed by noncompartmental pharmacokinetic analyses. The mean (±SD) plasma Cmax and Tmax for meloxicam (2.89 ± 0.48 μg/mL and 11.33 ± 4.12 h) were not much different from gabapentin at 10 mg/kg (2.87 ± 0.2 μg/mL and 8 ± 0 h). The mean (±SD) milk Cmax for meloxicam (0.41 ± 80.16 μg/mL) was comparable to gabapentin at 10 mg/kg (0.63 ± 0.13 μg/mL and 12 ± 6.69 h). The mean plasma and milk Cmax for gabapentin at 20 mg/kg P.O. were almost double the values at 10 mg/kg. The mean (±SD) milk to plasma ratio for meloxicam (0.14 ± 0.04) was lower than for gabapentin (0.23 ± 0.06). The results of this study suggest that milk from treated cows will have low drug residue concentration soon after plasma drug concentrations have fallen below effective levels.  相似文献   

13.
Soma, L. R., Uboh, C. E., Liu, Y., Li, X., Robinson, M .A., Boston, R. C., Colahan, P. T. Pharmacokinetics of dexamethasone following intra‐articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone. J. vet. Pharmacol. Therap.  36 , 181–191. This study investigated and compared the pharmacokinetics of intra‐articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax) and time to maximum concentration (Tmax). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6–35.4), 23.4 (13.5–73.0), and 46.9 (24.0–72.1) ng/mL, respectively. The Tmax for IAC, IAF, and IAS were 1.0 (0.75–4.0), 0.62 (0.5–1.0), and 0.25 (0.08–0.25) h, respectively. Median (range) elimination half‐lives for IA and IM administrations were 3.6 (3.0–4.6) h and 3.4 (2.9–3.7) h, respectively. A 3‐compartment model was fitted to the plasma dexamethasone concentration–time curve following the IV administration of DSP; alpha, beta, and gamma half‐lives were 0.03 (0.01–0.05), 1.8 (0.34–2.3), and 5.1 (3.3–5.6) h, respectively. Following the PO administration, the median absorption and elimination half‐lives were 0.34 (0.29–1.6) and 3.4 (3.1–4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1–3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO.  相似文献   

14.
Bimazubute, M., Cambier, C., Baert, K., Vanbelle, S., Chiap, P., Gustin, P. Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs. J. vet. Pharmacol. Therap. 34 , 176–183. The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)‐administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra‐high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter‐dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 μg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (μg/mL) can be predicted taking into account the OTC concentrations in plasma (μg/mL), according to the following equation: OTCnasal secretions = 0.28 OTCplasma?1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single‐dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non‐compartmental analysis. In plasma, the maximum concentration of drug (Cmax), the time at which this maximum concentration of drug (Tmax) was reached, the elimination half‐life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 μg/mL, 4.0, 5.1 h and 150 μg·h/mL. In nasal secretions, Cmax, Tmax, t½ and AUC were, respectively, 6.29 μg/mL, 4.0, 6.6 h and 51.1 μg·h/mL.  相似文献   

15.
Objective— To estimate maximum plasma concentration (Cmax) and time to maximum plasma (tmax) bupivacaine concentration after intra‐articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Study Design— Cross‐over design with a 2‐week washout period. Animals— Healthy Coon Hound dogs (n=8). Methods— Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration–time curves and estimate Cmax, Tmax and other pharmacokinetic variables for comparison of SI and CI. Results— Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (Cmax, 1.33±0.954 μg/mL) occurred at 11.37±4.546 minutes. For CI, mean Cmax (1.13±0.509 μg/mL) occurred at 10.37±4.109 minutes. The area under the concentration–time curve was smaller for SI (143.59±118.390 μg/mL × min) than for CI (626.502±423.653 μg/mL × min, P=.02) and half‐life was shorter for SI (61.33±77.706 minutes) than for CI (245.363±104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 μg/mL for SI and 2.3 μg/mL for CI. Conclusion— Intra‐articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean Cmax below that considered toxic and no systemic drug accumulation. Clinical Relevance— Intra‐articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra‐articular injection.  相似文献   

16.
Zhao, Z., Xue, F., Zhang, L., Zhang, K., Fei, C., Zheng, W., Wang, X., Wang, M., Zhao, Z., Meng, X. The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding ability in vitro. J. vet. Pharmacol. Therap. 33 , 147–153. The pharmacokinetics of tizoxanide (T), the active metabolite of nitazoxanide (NTZ), and its protein binding ability in goat plasma and in the solutions of albumin and α‐1‐acid‐glycoprotein were investigated. The plasma and protein binding samples were analyzed using a high‐performance liquid chromatography (HPLC) assay with UV detection at 360 nm. The plasma concentration of T was detectable in goats up to 24 h. Plasma concentrations vs. time data of T after 200 mg/kg oral administration of NTZ in goats were adequately described by one‐compartment open model with first order absorption. As to free T, the values of t1/2Ka, t1/2Ke, Tmax, Cmax, AUC, V/F(c), and Cl(s) were 2.51 ± 0.41 h, 3.47 ± 0.32 h, 4.90 ± 0.13 h, 2.56 ± 0.25 μg/mL, 27.40 ± 1.54 (μg/mL) × h, 30.17 ± 2.17 L/kg, and 7.34 ± 1.21 L/(kg × h), respectively. After β‐glucuronidase hydrolysis to obtain total T, t1/2ke, Cmax, Tmax, AUC increased, while the V/F(c) and Cl(s) decreased. Study of the protein binding ability showed that T with 4 μg/mL concentration in goat plasma and in the albumin solution achieved a protein binding percentage of more than 95%, while in the solution of α‐1‐acid‐glycoprotein, the percentage was only about 49%. This result suggested that T might have much more potent binding ability with albumin than with α‐1‐acid‐glycoprotein, resulting from its acidic property.  相似文献   

17.
An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys (Aquus astnus) intravenously (once at 10 mg/kg), intramuscularly and orally (both routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples were collected at predetermined times after each treatment and urine was sampled after intravenous drug administration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NFN over 45–60 s resulted in seizures, profuse sweating and tachycardia. The intravenous half-life (t1/2β was 209 ± 36 min, the apparent volume of distribution (Vd(area)) was 3.34 ± 0.58 L/kg, the total body clearance (ClE) was 1.092 ± 0.123 ± 10--2mL/min/kg and the renal clearance (C1R) was 0.411 ± 0.057 ± 10--2mL/min/kg. Oral bioavailability was rather poor (9.6% and 6.4% for the 10 and 20 mg/kg doses respectively). Multiple oral treatments did not result in any clinical gastrointestinal disturbances. After intramuscular administration (20 mg/kg), serum NFN concentrations > 0.25 μg/mL (necessary to inhibit the majority of gram-negative bacteria isolated from horses) were maintained for 12 h. The intramuscular bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg doses respectively. After multiple dosing some local swelling was observed at the injection site. About 40% of the intravenous dose was recovered in the urine as parent drug. The results of comprehensive haematological and blood biochemistry tests indicated no abnormal findings except elevation in serum CPK (creatine phosphokinase) values after multiple intramuscular dosing. On the basis of the in vitro-determined minimum inhibitory concentrations of the drug and serum concentrations after multiple dosing, the suggested intramuscular dosage schedules for the treatment of gram-negative bacterial infections in Equidae are 10 mg/kg every 12 h or 20 mg/kg every 24 h.  相似文献   

18.
Yamarik, T. A., Wilson, W. D., Wiebe, V. J., Pusterla, N., Edman, J., Papich, M. G. Pharmacokinetics and toxicity of ciprofloxacin in adult horses. J. vet. Pharmacol. Therap. 33 , 587–594. Using a randomized, cross‐over study design, ciprofloxacin was administered i.g. to eight adult mares at a dose of 20 mg/kg, and to seven of the eight horses at a dose of 5 mg/kg by bolus i.v. injection. The mean C0 was 20.5 μg/mL (±8.8) immediately after i.v. administration. The Cmax was 0.6 μg/mL (±0.36) at Tmax 1.46 (±0.66) h after the administration of oral ciprofloxacin. The mean elimination half‐life after i.v. administration was 5.8 (±1.6) h, and after oral administration the terminal half‐life was 3.6 (±1.7) h. The overall mean systemic availability of the oral dose was 10.5 (±2.8)%. Transient adverse effects of mild to moderate severity included agitation, excitement and muscle fasciculation, followed by lethargy, cutaneous edema and loss of appetite developed in all seven horses after i.v. administration. All seven horses developed mild transient diarrhea at 36–48 after i.v. dosing. All eight horses dosed intragastrically experienced adverse events attributable to ciprofloxacin administration. Adverse events included mild transient diarrhea to severe colitis, endotoxemia and laminitis necessitating euthanasia of three horses on humane grounds. The high incidences of adverse events preclude oral and rapid i.v. push administration of ciprofloxacin.  相似文献   

19.
The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean ± SD): AUC(0–∞) 4.20 ± 1.66 μg·h/mL; Cmax 6.64 ± 1.38 μg/mL; Vz 4.80 ± 0.91 L/kg; Clt 2.64 ± 0.84 L/h·kg; t½λ 1.35 ± 0.40 h and MRT 1.50 ± 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean ± SD): Cmax, 0.30 ± 0.17 and 0.17 ± 0.09 μg/mL; tmax, 1.75 ± 0.76 and 0.69 ± 0.30 h; t½λ, 2.92 ± 0.79 and 1.53 ± 1.28 h and MRT, 5.10 ± 1.12 and 2.56 ± 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC90 = 0.5 μg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.  相似文献   

20.
The in-vitro activity of enrofloxacin against 117 strains of bacteria isolated from bustards was determined. Minimum inhibitory concentrations for 72% of the Proteus spp., E. coli, Salmonella spp. and Klebsiella spp. (n = 61) and for 48% of the Streptococci spp. and Staphylococci spp. (n = 31) were 0.5 μ g/mL. The minimum inhibitory concentration (MIC) of 76% of Pseudomonas spp. (n = 25) was 2 μg/mL. Fourteen strains were resistant to concentrations 128 μg/mL. The elimination half-lives (t½ elim β) (mean± SEM) of 10 mg/kg enrofloxacin in eight houbara bustards (Chlamydotis undulata) were 6.80± 0.79, 6.39± 1.49 and 5.63± 0.54 h after oral (p.o.), intramuscular (i.m.) and intravenous (i.v.) administration, respectively. Enrofloxacin was rapidly absorbed from the bustard gastro-intestinal tract and maximum plasma concentrations of 1.84± 0.16 μg/mL were achieved after 0.66± 0.05 h. Maximum plasma concentration after i.m. administration of 10 mg/kg was 2.75± 0.11 μg/mL at 1.72± 0.19 h. Maximum plasma concentration after i.m. administration of 15 mg/kg in two birds was 4.86 μg/mL. Bioavailability was 97.3± 13.7% and 62.7± 11.1% after i.m. and oral administration, respectively. Plasma concentrations of enrofloxacin 0.5 μg/mL were maintained for at least 12 h for all routes at 10 mg/kg and for 24 h after i.m. administration at 15 mg/kg. Plasma enrofloxacin concentrations were monitored during the first 3 days of treatment in five houbara bustards and kori bustards (Ardeotis kori) with bacterial infections receiving a single daily i.m. injection of 10 mg/kg for 3 days. The mean plasma enrofloxacin concentrations in the clinical cases at 27 and 51 h (3.69 and 3.86 μg/mL) and at 48 h (0.70 μg/mL) were significantly higher compared with the 3 h and 24 h time intervals from clinically normal birds. The maximum plasma concentration (Cmax)/MIC ratio was ranked i.v. (10/mg/kg) > i.m. (15 mg/kg) > i.m. (10 mg/kg) > oral (10 mg/kg), but it was only higher than 8:1 for i.v and i.m. administrations of enrofloxacin at 10 mg/kg and 15 mg/kg, respectively, against a low MIC (0.5 μg/mL). A dosage regimen of 10 mg/kg repeated every 12 h, or 15 mg/kg repeated every 24 h, would be expected to give blood concentrations above 0.5 μg/mL and hence provide therapeutic response in the bustard against a wide range of bacterial infections.  相似文献   

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