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1.
The pharmacokinetics of thiamphenicol in lactating cows   总被引：2，自引：0，他引：2  
The pharmacokinetics of thiamphenicol were studied after intravenous and intramuscular administration of 25 mg/kg body weight in lactating cows. Distribution (t 1/2) and elimination (t 1/2) half-lives of 6.10±1.39 min and 1.60±0.30 h, respectively, were obtained after intravenous administration. The body clearance was 3.9±0.077 ml/kg per min and the apparent volume of distribution was 1220.79±256.67 ml/kg. The rate at which thiamphenicol appeared in the milk, as indicated by the penetration half-life (t 1/2P) (serum to quarters), was found to be 36.89±11.14 min. The equivalent elimination half-life (t 1/2E) (quarters to serum) from the milk was 3.62±1.06 h and the peak thiamphenicol concentration in the milk was 23.09±3.42 µg/ml at 2.5±0.32 h.After intramuscular injection, the elimination half-life was 2.2±0.40 h, the absorption half-life was 4.02±1.72 min and the peak concentration in the serum was 30.90±5.24 µg/ml at 23±8.4 min. The bioavailability after intramuscular administration approached 100%. The penetration half-life was 50.59±6.87 min, the elimination half-life was 5.91±4.97 h and the mean peak concentration in the milk was 17.37±2.20 µg/ml at 3.4±0.22 h.Abbreviations AUC area under the concentration-time curve - CAP chloramphenicol - C max peak concentration - IM intramuscular - IV intravenous - TAP thiamphenicol - t 1/2 distribution half-life - t 1/2 elimination half-life - V c volume of central compartment - V d volume of distribution  相似文献   

2.
The pharmacokinetics of oleandomycin OLD) after intravenous and oral administration, both alone and after intramuscular pretreatment with metamizole or dexamethasone, were studied in healthy dogs. After intravenous injection of OLD alone 10 mg/kg as bolus), the elimination half-life t 1/2, volume of distribution V d, area), body clearance CLB) and area under the concentration-time curve AUC) were 1.60 h, 1.11 L/kg, 7.36 ml/kg)/min and 21.66 µg h/ml, respectively. There were no statistically significant differences following pretreatment with metamizole or dexamethasone. After oral administration of OLD alone, the t frac12;, maximum plasma concentrations C max), time of C max t max), mean absorption time MAT) and absolute bioavailability F abs) were 1.68 h, 5.34 µg/ml, 1.5 h, 1.34 h and 84.29%, respectively. Pretreatment with metamizole caused a significantly decreased value for C max 2.93 µg/ml) but the MAT value 2.23 h) was significantly increased. Statistically significant changes in the pharmacokinetic parameters of OLD following oral administration were also observed as a result of pretreatment with dexamethasone. The C max was increased 8.24 µg/ml) and the t max 0.5 h) and MAT 0.45 h) were lower.  相似文献   

3.
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   

4.
The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (C max) of ivermectin administered in the standard tablet formulation at 6 and 100 µg/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics.C max and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 µg/kg. Furthermore,C max was similar following administration of radiolabelled ivermectin at 6 µg/kg in either a beef-based chewable formulation or in the standard tablet formulation.  相似文献   

5.
Thiamphenicol (TP) pharmacokinetics were studied in Japanese quails (Coturnix japonica) following a single intravenous (IV) and oral (PO) administration at 30 mg/kg BW. Concentrations of TP were determined with HPLC and were analyzed by a noncompartmental method. After IV injection, elimination half-life (t1/2λz), total body clearance (Cltot) volume of distribution at steady state (Vdss), and mean residence time (MRT) of TP were 3.83 hr, 0.19 L/hr/kg, 0.84 L/kg, and 4.37 hr, respectively. After oral administration of TP, the peak plasma concentration (Cmax) was 19.81 μg/ml and was obtained at 2.00 hr (tmax) postadministration. Elimination half-life (t1/2λz) and mean absorption time (MAT) were 4.01 hr and 1.56 hr, respectively. The systemic bioavailability following oral administration of TP was 78.10%. TP therapy with an oral dosage of 30 mg/kg BW is suggested for a beneficial clinical effect in quails.  相似文献   

6.
The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t 1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t 1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V dss), mean residence time (MRT) and total systemic clearance (ClB) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t max) was 2.3±0.7 h. The absorption half-life (t 1/2 ka), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.  相似文献   

7.
Florfenicol, a monofluorinated analogue of thiamphenicol, has a broad antibacterial spectrum. The pharmacokinetics of florfenicol was studied following a single intravenous (i.v.) or intramuscular (i.m.) injection at a dose of 20 mg/kg body weight in healthy male camels, sheep and goats. The concentration of florfenicol in plasma was determined using a microbiological assay. Pharmacokinetic analysis was performed using a two-compartment open model. Following i.m. administration, the maximum plasma concentration of florfenicol (C max) reached in camels, sheep and goats was 0.84±0.08, 1.04±0.10 and 1.21±0.10 g/ml, respectively, the the time required to reach C max (t max) in the same three respective species was 1.51±0.14, 1.44±0.10 and 1.21±0.10 h. The terminal half-life (t 1/2) and the fraction of the drug absorbed (F%) in camels, sheep and goats were 151.3±16.33, 137.0±12.16 and 127.4±11.0 min, and 69.20%±7.8%, 65.82%±6.7% and 60.88%±5.9%, respectively. The MRT in the same three respective species was 4.01±0.45, 3.42±0.39 and 2.98±0.32 h. Following i.v. administration, the terminal half-life (t 1/2) and total body clearance (ClB) in camels, sheep and goats were 89.5±9.2, 78.8±8.3 and 71.1±8.9 min and 0.33±0.04, 0.30±0.03 and 0.27±0.03 L/h per kg, respectively. The area under the curve (AUC0–) and the mean residence time (MRT) in the same three respective species were 60.61±6.98, 62.45±6.56 and 74.07±7.85 g/ml per h, and 2.71±0.31, 2.34±0.25 and 2.11±0.23 h. These data suggest that sheep and goats absorb and clear florfenicol to a broadly similar extent, but the rate and extent of absorption of the drug tends to be higher in camels. Drug treatment caused no clinically overt adverse effects. Plasma enzyme activities and metabolites indicative of hepatic and renal functions measured 1, 2, 4 and 7 days following the drug treatment were within the normal range, indicating that the drug is safe at the dose used.  相似文献   

8.
A study was conducted on the pharmacokinetics and therapeutic efficacy of triclabendazole at three low dose rates of 0.5, 1.0 and 1.5 mg/kg body weight in buffaloes experimentally infected with Fasciola gigantica. The pharmacokinetics were compared with the effects of a single intraruminal dose at 24.0 mg/kg body weight in uninfected buffaloes. At all three dose rates, an equilibrium between the absorption of triclabendazole and the disposition of its metabolites was observed by days 3 and 4 and remained almost unchanged thereafter. Continuous daily dosing at 1.5 mg/kg body weight proved to be efficacious against liver fluke infection in buffaloes.Abbreviations TCBZ triclabendazole - p.i. post-infection - HPLC high-performance liquid chromatography - TCBZ-SO triclabendazole sulphoxide - TCBZ-SO2 triclabendazole sulphone - C max peak concentration in plasma - T max time to reach C max - AUC area under the concentration-time curve - t 1/2 elimination half-life - epg eggs per gram  相似文献   

9.
The aim of this study was to elucidate some of the pharmacokinetic parameters of pefloxacin in lactating goats (n = 5) following intravenous (i.v.) or intramuscular (i.m.) injections of 10 mg/kg bw. Serially obtained serum, milk and urine samples were collected at precise time intervals, and the drug concentrations were assayed using a microbiological assay. A two-compartment open model best described the decrease of pefloxacin concentration in the serum after intravenous administration. The maximum serum concentration (C p 0 ) was 8.4±0.48 g/ml; elimination half-life (t 1/2) was 1.6±0.3 h; total body clearance (Cltot) was 3.6±0.3 L/kg/h; steady-state volume of distribution (V dss) was 5.14±0.21 L/kg; and the area under the curve (AUC) was 2.78±0.22 g.ml/h. Pefloxacin was absorbed rapidly after i.m. injection with an absorption half-life (t 1/2ab) of 0.32±0.02 h. The peak serum concentration (C max) of 0.86±0.08 g/ml was attained at 0.75 h (T max). The absolute bioavailability after i.m. administration was 70.63±1.13% and the serum protein-bound fraction ranged from 7.2% to 14.3%, with an average value of 9.8±1.6%. Penetration of pefloxacin from the blood into the milk was rapid and extensive, and the pefloxacin concentration in milk exceeded that in serum from 1 h after administration. The drug was detected in milk and urine for 10 and 72 h, respectively; no samples were taken after 72 h.  相似文献   

10.
Bicozamycin was dissolved in water and administered to pigs by stomach tube at 40 mg/kg once daily for 7 consecutive days. The plasma concentration was determined on days 1 and 7 of the dosing period. The mean (± SD) peak plasma concentrations were 2.06±0.36 µg/ml at 3.08±0.80 h on day 1 and 2.36±1.32 µg/ml at 2.80±0.74 h on day 7, the elimination half-lives being 3.80±0.92 h and 2.43±1.41 h, respectively. The mean areas under the plasma concentration-time curves were 15.88±2.18 (µg h)/ml on day 1 and 12.31±6.98 (µg h)/ml on day 7. These pharmacokinetic parameters did not differ between days 1 and 7, suggesting that there was no accumulation in the plasma after consecutive oral dosing. The residues in kidney, liver and muscle were examined in pigs slaughtered on days 1, 3 and 5 after the last dosing. One day after withdrawal, residues were found in the kidneys of all three pigs examined, at a mean concentration of 0.26 µg/g, and in muscle from one pig, but not in liver from any of the pigs. Bicozamycin was not detected in any of the samples taken 3 or 5 days after withdrawal.Abbreviations AUC area under the plasma concentration-time curve - C max peak concentration - T max time of the peak - t 1/2 elimination half-life  相似文献   

11.
The pharmacokinetics and bioavailability of gentamicin sulphate (5 mg/kg body weight) were studied in 50 female broiler chickens after single intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.) and oral administration. Blood samples were collected at time 0 (pretreatment), and at 5, 15 and 30 min and 1, 2, 4, 6, 8, 12, 24 and 48 h after drug administration. Gentamicin concentrations were determined using a microbiological assay and Bacillus subtillis ATCC 6633 as a test organism. The limit of quantification was 0.2 μg/ml. The plasma concentration–time curves were analysed using non-compartmental methods based on statistical moment theory. Following i.v. administration, the elimination half-life (t 1/2β), the mean residence time (MRT), the volume of distribution at steady state (V ss), the volume of distribution (V d,area) and the total body clearance (ClB) were 2.93 ± 0.15 h, 2.08 ± 0.12 h, 0.77 ± 0.05 L/kg, 1.68 ± 0.39 L/kg and 5.06 ± 0.21 ml/min per kg, respectively. After i.m. and s.c. dosing, the mean peak plasma concentrations (C max) were 11.37 ± 0.73 and 16.65 ± 1.36 μg/ml, achieved at a post-injection times (t max) of 0.55 ± 0.05 and 0.75 ± 0.08 h, respectively. The t 1/2β was 2.87 ± 0.44 and 3.48 ± 0.37 h, respectively after i.m. and s.c. administration. The V d,area and ClB were 1.49 ± 0.21 L/kg and 6.18 ± 0.31 ml/min per kg, respectively, after i.m. administration and were 1.43 ± 0.19 L/kg and 4.7 ± 0.33 ml/min per kg, respectively, after s.c. administration. The absolute bioavailability (F) of gentamicin after i.m. administration was lower (79%) than that after s.c. administration (100%). Substantial differences in the resultant kinetics data were obtained between i.m. and s.c. administration. The in vitro protein binding of gentamicin in chicken plasma was 6.46%.  相似文献   

12.
The pharmacokinetics of a slow-release theophylline formulation was investigated following intravenous and oral administration at 10 mg/kg in horses. A tricompartmental model was selected to describe the intravenous plasma profile. The elimination half-life (t1/2) was 16.91 ± 0.93 h, the apparent volume of distribution (V d) was 1.35 ± 0.18 L/kg and the body clearance (ClB) was 0.061 ± 0.009 L kg–1 h. After oral administration the half-life of absorption was 1.24 ± 0.30 h, and the calculated bioavailability was above 100%. Thet1/2 after oral administration was 18.51 ± 1.75 h, only a little longer than that after intravenous administration. The slow release formulation did not exhibit any advantage in prolonging thet1/2 of theophylline in the horse.  相似文献   

13.
Five lactating cows were given benzydamine hydrochloride by rapid intravenous (0.45 mg/kg) and by intramuscular (0.45 and 1.2 mg/kg) injection in a crossover design. The bioavailability, pharmacokinetic parameters and excretion in milk of benzydamine were evaluated. After intravenous administration, the disposition kinetics of benzydamine was best described using a two-compartment open model. Drug disposition and elimination were fast (t 1/2: 11.13±3.76 min;t 1/2: 71.98±24.75 min; MRT 70.69±11.97 min). Benzydamine was widely distributed in the body fluids and tissues (V d(area): 3.549±1.301 L/kg) and characterized by a high value for body clearance (33.00±5.54 ml/kg per min). After intramuscular administration the serum concentration-time curves fitted a one-compartment open model. Following a dose of 0.45 mg/kg, theC max value was 38.13±4.2 ng/ml at at max of 67.13±4.00 min; MAT and MRT were 207.33±22.64 min and 278.01±12.22 min, respectively. Benzydamine bioavailability was very high (92.07%±7.08%). An increased intramuscular dose (1.2 mg/kg) resulted in longer serum persistence (MRT 420.34±86.39 min) of the drug, which was also detectable in milk samples collected from both the first and second milking after treatment.Abbreviations HPLC high-pressure liquid chromatography - IC50 concentration to inhibit the activity of an organism by 50% - IM intramuscular(ly) - IV intravenous(ly) - NSAID non-steroidal antiinflammatory drugs - pK a negative logarithm of the ionization constant (K a) of a drug; other abbreviations are listed in footnotes to tables  相似文献   

14.
The disposition kinetics of fenvalerate were studied in goats after dermal application of 100 ml of 0.25% (w/v) solution. The insecticide persisted in the blood for 72 h. The mean (±SEM) V d(area) and apparent t 1/2 () were 9.92±1.44 L/kg and 17.51±2.65 h, while the AUC and ClB values were respectively 82.15±7.40 g h/ml and 0.56±0.05 L/(kg h). Four days after the dermal application, the highest concentration of fenvalerate residues was found in the adrenal gland, followed by the biceps muscle, omental fat, liver, kidney, lung and cerebrum in that order. Fenvalerate caused hyperglycaemia but had no effect on serum protein and cholesterol levels. Serum acetylcholinesterase activities were increased after 24 h but were below the initial values from 48 to 120 h.Abbreviations Ache acetylcholinestase - AUC total area under the blood insecticide concentration-versus-time curve - ClB total body clearance - GLC gas-liquid chromatography - t 1/2() apparent elimination half-life - V d(area) apparent volume of insecticide distribution based on area method  相似文献   

15.
Tulathromycin is a triamilide antibiotic that maintains therapeutic concentrations for an extended period of time. The drug is approved for the treatment of respiratory disease in cattle and swine and is occasionally used in goats. To investigate the pharmacokinetics of tulathromycin in meat goats, 10 healthy Boer goats were administered a single 2.5 mg/kg subcutaneous dose of tulathromycin. Plasma concentrations were measured by ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC–MS/MS) detection. Plasma maximal drug concentration (Cmax) was 633 ± 300 ng/ml (0.40 ± 0.26 h post-subcutaneous injection). The half-life of tulathromycin in goats was 110 ± 19.9 h. Tulathromycin was rapidly absorbed and distributed widely after subcutaneous injection 33 ± 6 L/kg. The mean AUC of the group was 12,500 ± 2020 h ng/mL for plasma. In this study, it was determined that the pharmacokinetics of tulathromycin after a single 2.5 mg/kg SC injection in goats were very similar to what has been previously reported in cattle.  相似文献   

16.
The pharmacokinetics and oral bioavailability of tylosin tartrate and tylosin phosphate were carried out in broiler chickens according to a principle of single dose, random, parallel design. The two formulations of tylosin were given orally and intravenously at a dose level of 10 mg/kg b.w to chicken after an overnight fasting (n = 10 chickens/group). Serial blood samples were collected at different time points up to 24 h postdrug administration. A high performance liquid chromatography method was used for the determination of tylosin concentrations in chicken plasma. The tylosin plasma concentration's time plot of each chicken was analyzed by the 3P97 software. The pharmacokinetics of tylosin was best described by a one‐compartmental open model 1st absorption after oral administration. After intravenous administration the pharmacokinetics of tylosin was best described by a two‐compartmental open model, and there were no significant differences between tylosin tartrate and tylosin phosphate. After oral administration, there were significant differences in the Cmax (0.18 ± 0.01, 0.44 ± 0.09) and AUC (0.82 ± 0.05, 1.57 ± 0.25)between tylosin phosphate and tylosin tartrate. The calculated oral bioavailability (F) of tylosin tartrate and tylosin phosphate were 25.78% and 13.73%, respectively. Above all, we can reasonably conclude that, the absorption of tylosin tartrate is better than tylosin phosphate after oral administration.  相似文献   

17.
The pharmacokinetics of allopurinol were studied in Dalmatian dogs. Eight dogs were given allopurinol orally at a dose of 10 mg/kg for seven doses prior to sample collection. After a period of at least two weeks, four of these dogs and four additional Dalmatians were later given a single intravenous (i.v.) dose of allopurinol (6 mg/kg) prior to sample collection.Allopurinol was found to follow first-order absorption and elimination kinetics. In the i.v. kinetic study, the elimination constant (Kel) = 0.31±0.03 per h, the half-life (t½) = 2.22±0.20 h, the initial concentration (C0) = 5.26±0.34 μg/mL and the specific volume (Vd) = 1.14±0.07 L/kg. Clearance of allopurinol was estimated to be 0.36±0.03 L/kg·h. In the oral kinetic study, the absorption rate constant (Kab) = 1.06±0.13 per h, the elimination rate constant (Kel) = 0.26±0.01 per h, the absorption half-life (t½ab) = 0.66±0.06 h, and the elimination half-life (t½el) = 2.69±0.14 h. Peak plasma concentrations (Cmax) = 6.43±0.18 μg/mL were obtained within 1 to 3 h (mean time of maximum concentration (Tmax) = 1.9±0.1 h). The volume of distribution corrected by the fraction of dose absorbed (Vd/F) was estimated to be 1.17±0.07 L/kg.Good agreement was obtained between mean kinetic parameters in the oral and i.v. studies. There was little variation between individual dogs in the i.v. study, whereas the rate of absorption and elimination of orally administered allopurinol was more varied among individual dogs. Because of this, and the fact that the magnitude of hyperuricosuria varies among Dalmatians, it is not possible to specify an exact dose of allopurinol that will effectively lower the urinary uric acid concentration to acceptable values in all Dalmatians with hyperuricosuria; rather, the dose must be titrated to the needs of each dog.  相似文献   

18.
The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study using three groups (n = 4) of male and female Friesian calves after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg body weight. Drug concentration in plasma was determined by high-performance liquid chromatography using fluorescence detection. The plasma concentration–time data following i.v. administration were best fitted to a two-compartment open model and those following i.m. and s.c. routes were best fitted using one-compartment open model. The collected data were subjected to a computerized kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives (t 1/2β) were 5.56 ± 0.33 h, 6.12 ± 0.42 h and 7.26 ± 0.6 h, respectively. The steady-state volume of distribution (V dss) was 1.12 ± 0.09 L/kg and total body clearance (ClB) was 2.19 ± 0.1 ml/(min. kg). The absorption half lives (t 1/2ab) were 0.38 ± 0.027 h and 2.1 ± 0.09 h, with systemic bioavailabilities (F) of 96.5% ± 6.4% and 84% ± 5.5% after i.m. and s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma concentrations (C max) of 3.38 ± 0.13 μg/ml and 2.18 ± 0.12 μg/ml were attained after (t max) 1.22 ± 0.20 h and 3.7 ± 0.52 h. The MIC90 of difloxacin for Mannheimia haemolytica was 0.29 ± 0.04 μg/ml. The AUC/MIC90 and C max/MIC90 ratios for difloxacin following i.m. administration were 120 and 11.65, respectively and following s.c. administration were 97.58 and 7.51, respectively. Difloxacin was 31.7–36.8% bound to calf plasma protein. Since fluoroquinolones display concentration-dependent activities, the doses of difloxacin used in this study are likely to involve better pharmacodynamic characteristics that are associated with greater clinical efficacy following i.m. administration than following s.c. administration.  相似文献   

19.
The pharmacokinetics, PK/PD ratios, and Monte Carlo modeling of enrofloxacin HCl‐2H2O (Enro‐C) and its reference preparation (Enro‐R) were determined in cows. Fifty‐four Jersey cows were randomly assigned to six groups receiving a single IM dose of 10, 15, or 20 mg/kg of Enro‐C (Enro‐C10, Enro‐C15, Enro‐C20) or Enro‐R. Serial serum samples were collected and enrofloxacin concentrations quantified. A composite set of minimum inhibitory concentrations (MIC) of Leptospira spp. was utilized to calculate PK/PD ratios: maximum serum concentration/MIC (Cmax/MIC90) and area under the serum vs. time concentration of enrofloxacin/MIC (AUC0‐24/MIC90). Monte Carlo simulations targeted Cmax/MIC = 10 and AUC0‐24/MIC = 125. Mean Cmax obtained were 6.17 and 2.46 μg/ml; 8.75 and 3.54 μg/ml; and 13.89 and 4.25 μg/ml, respectively for Enro‐C and Enro‐R. Cmax/MIC90 ratios were 6.17 and 2.46, 8.75 and 3.54, and 13.89 and 4.25 for Enro‐C and Enro‐R, respectively. Monte Carlo simulations based on Cmax/MIC90 = 10 indicate that only Enro‐C15 and Enro‐C20 may be useful to treat leptospirosis in cows, predicting a success rate ≥95% when MIC50 = 0.5 μg/ml, and ≥80% when MIC90 = 1.0 μg/ml. Although Enro‐C15 and Enro‐C20 may be useful to treat leptospirosis in cattle, clinical trials are necessary to confirm this proposal.  相似文献   

20.
Menge, M., Rose, M., Bohland, C., Zschiesche, E., Kilp, S., Metz, W., Allan, M., Röpke, R., Nürnberger, M. Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle). J. vet. Pharmacol. Therap.  35 , 550–559. The pharmacokinetics of tildipirosin (Zuprevo® 180 mg/mL solution for injection for cattle), a novel 16‐membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (Cmax) was 0.7 μg/mL. Tmax was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRTlast) and terminal half‐life (T1/2) was 6 and 9 days, respectively. A strong dose–response relationship with no significant sex effect was shown for both Cmax and area under the plasma concentration–time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUClast) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (Vz) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time–concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T1/2 in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination.  相似文献   

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