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1.
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   

2.
The objective of this study was to investigate the pharmacokinetics of cefquinome following single intramuscular (IM) administration in six healthy male buffalo calves. Cefquinome was administered intramuscularly (2 mg/kg bodyweight) and blood samples were collected prior to drug administration and up to 24 hr after injection. No adverse effects or changes were observed after the IM injection of cefquinome. Plasma concentrations of cefquinome were determined by high‐performance liquid chromatography. The disposition of plasma cefquinome is characterized by a mono‐compartmental open model. The pharmacokinetic parameters after IM administration (mean ± SE) were Cmax 6.93 ± 0.58 μg/ml, Tmax 0.5 hr, t½kα 0.16 ± 0.05 hr, t½β 3.73 ± 0.10 hr, and AUC 28.40 ± 1.30 μg hr/ml after IM administration. A dosage regimen of 2 mg/kg bodyweight at 24‐hr interval following IM injection of cefquinome would maintain the plasma levels required to be effective against the bacterial pathogens with MIC values ≤0.39 μg/ml. The suggested dosage regimen of cefquinome has to be validated in the disease models before recommending for clinical use in buffalo calves.  相似文献   

3.
The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 ± 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutaneously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concentrations of CFQ were measured using the HPLC‐UV method. Pharmacokinetic parameters were calculated using non‐compartmental methods. The elimination half‐life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the single SC administration was 123.51 ± 11.54%. The area under the curve (AUC0‐∞) and peak concentration following repeated doses (last dose) were higher than those observed after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is ≤1.0 μg/ml in sheep.  相似文献   

4.
Ketoprofen is a nonsteroidal anti‐inflammatory and analgesic agent that nonselectively inhibits cyclooxygenase, with both COX‐1 and COX‐2 inhibition. Recent studies on COX receptor expression in reptiles suggest that nonselective COX inhibitors may be more appropriate than more selective inhibitors in some reptiles, but few pharmacokinetic studies are available. The goal of this study was to determine single‐ and multidose (three consecutive days) pharmacokinetics of racemic ketoprofen administered intravenously and intramuscularly at 2 mg/kg in healthy juvenile loggerhead turtles (Caretta caretta). The S‐isomer is the predominant isomer in loggerhead sea turtles, similar to most mammals, despite administration of a 50:50 racemic mixture. Multidose ketoprofen administration demonstrated no bioaccumulation; therefore, once‐daily dosing will not require dose adjustment over time. S‐isomer pharmacokinetic parameters determined in this study were Cmax of 10.1 μg/ml by IM injection, C0 of 13.4 μg/ml by IV injection, AUC of 44.7 or 69.4 μg*hr/ml by IM or IV injection, respectively, and T½ of 2.8 or 3.6 hr by IM or IV injection, respectively. Total ketoprofen plasma concentrations were maintained for at least 12 hr above concentrations determined to be effective for rats and humans. A dose of 2 mg/kg either IM or IV every 24 hr is likely appropriate for loggerhead turtles.  相似文献   

5.
The pharmacokinetic properties of the fluoroquinolone levofloxacin (LFX) were investigated in six dogs after single intravenous, oral and subcutaneous administration at a dose of 2.5, 5 and 5 mg/kg, respectively. After intravenous administration, distribution was rapid (T½dist 0.127 ± 0.055 hr) and wide as reflected by the volume of distribution of 1.20 ± 0.13 L/kg. Drug elimination was relatively slow with a total body clearance of 0.11 ± 0.03 L kg?1 hr?1 and a T½ for this process of 7.85 ± 2.30 hr. After oral and subcutaneous administration, absorption half‐life and Tmax were 0.35 and 0.80 hr and 1.82 and 2.82 hr, respectively. The bioavailability was significantly higher (p ? 0.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC24 hr/MIC and Cmax/MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5 mg/kg), subcutaneously (5 mg/kg) or orally (5 mg/kg) is efficacious against Gram‐negative bacteria with MIC values of 0.1 μg/ml. For Gram‐positive bacteria with MIC values of 0.5 μg/kg, only SC and PO administration at a dosage of 5 mg/kg showed to be efficacious. MIC‐based PK/PD analysis by Monte Carlo simulation indicates that the proposed dose regimens of LFX, 5 and 7.5 mg/kg/24 hr by SC route and 10 mg/kg/24 hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S. aureus strains with MIC ≤ 0.5 μg/ml and E. coli strains with MIC values ≤0.125 μg/ml.  相似文献   

6.
The purpose of this study was to evaluate the pharmacokinetics of cefquinome (CFQ ) following single intravenous (IV ) or intramuscular (IM ) injections of 2 mg/kg body weight in red‐eared slider turtles. Plasma concentrations of CFQ were determined by high‐performance liquid chromatography and analyzed using noncompartmental methods. The pharmacokinetic parameters following IV injection were as follows: elimination half‐life (t 1/2λz) 21.73 ± 4.95 hr, volume of distribution at steady‐state (V dss) 0.37 ± 0.11 L/kg, area under the plasma concentration–time curve (AUC 0–∞) 163 ± 32 μg hr?1 ml?1, and total body clearance (ClT) 12.66 ± 2.51 ml hr?1 kg?1. The pharmacokinetic parameters after IM injection were as follows: peak plasma concentration (C max) 3.94 ± 0.84 μg/ml, time to peak concentration (T max) 3 hr, t 1/2λz 26.90 ± 4.33 hr, and AUC 0–∞ 145 ± 48 μg hr?1 ml?1. The bioavailability after IM injection was 88%. Data suggest that CFQ has a favorable pharmacokinetic profile with a long half‐life and a high bioavailability in red‐eared slider turtles. Further studies are needed to establish a multiple dosage regimen and evaluate clinical efficacy.  相似文献   

7.
The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (Cmax) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half‐life (T1/2β) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration–time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration.  相似文献   

8.
The aim of this study was to determine the pharmacokinetics and prostaglandin E2 (PGE2) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight adult female Boer goats. A dose of 2.2 mg/kg was administered intravenously (IV) and 3.3 mg/kg administered TD using a cross‐over design. Plasma flunixin concentrations were measured by LC‐MS/MS. Prostaglandin E2 concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE2 concentrations decreased after flunixin meglumine for both routes of administration. Mean λz‐HL after IV administration was 6.032 hr (range 4.735–9.244 hr) resulting from a mean Vz of 584.1 ml/kg (range, 357.1–1,092 ml/kg) and plasma clearance of 67.11 ml kg?1 hr?1 (range, 45.57–82.35 ml kg?1 hr?1). The mean Cmax, Tmax, and λz‐HL for flunixin following TD administration was 0.134 μg/ml (range, 0.050–0.188 μg/ml), 11.41 hr (range, 6.00–36.00 hr), and 43.12 hr (15.98–62.49 hr), respectively. The mean bioavailability for TD flunixin was calculated as 24.76%. The mean 80% inhibitory concentration (IC80) of PGE2 by flunixin meglumine was 0.28 μg/ml (range, 0.08–0.69 μg/ml) and was only achieved with IV formulation of flunixin in this study. The PK results support clinical studies to examine the efficacy of TD flunixin in goats. Determining the systemic effects of flunixin‐mediated PGE2 suppression in goats is also warranted.  相似文献   

9.
The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.  相似文献   

10.
The pharmacokinetic properties and tissue distribution of enrofloxacin (EF) were investigated after single intramuscular (i.m.) dose of 10 mg/kg body weight (b.w.) in Pacific white shrimp at 22 to 25°C. EF and its metabolite ciprofloxacin (CF) were determined by high‐performance liquid chromatography. After i.m. administration, EF was absorbed quickly, and the peak of EF concentration (Cmax) reached at first time point in hemolymph. The volume of distribution Vd(area) of EF was 3.84 L/kg, indicating that the distribution of EF was good. The area under the concentration–time curve (AUC) of EF was 90.1 and 274.2 μg hr/ml in muscle and hepatopancreas, respectively, which was higher than 75.8 μg hr/ml in hemolymph. The EF elimination was slow in muscle and hepatopancreas with the half‐life (T1/2β) of 52.3 and 75.8 hr, respectively. CF, the mainly metabolite of EF, was detected in hemolymph, muscle and hepatopancreas. The Cmax was 0.030, 0.013 and 0.218 μg/ml, respectively. Based on a minimum inhibitory concentration (MIC) of 0.006–0.032 μg/ml for susceptible strains, EF i.m. injected at a dose 10 mg/kg could be efficacious against common pathogenic bacteria of Pacific white shrimp.  相似文献   

11.
The pharmacokinetics and bioavailability of levamisole were determined in red‐eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three‐way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high‐performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half‐life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr?1 kg?1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 μg/ml, respectively, with 0.5 hr of Tmax. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t1/2?z, can be recommended as an effective way for treating nematodes in turtles.  相似文献   

12.
Fluoroquinolone antibacterial drugs are currently used in reptilian medicine because of their broad spectrum of activity including the most frequent pathogens of these species. The disposition kinetics of marbofloxacin (MBX) at a single dose of 2 mg/kg were determined in healthy red-eared sliders after intravenous (IV) and intramuscular (IM) administration. The influence of renal portal system on the bioavailability of the drug was investigated by using forelimb and hindlimb as IM injection sites. Apparent volume of distribution at steady-state (Vss) and systemic clearance (Cl) of marbofloxacin after IV administration were estimated to be 48.21 ± 5.42 ml/kg and 23.38 ± 2.90 ml/hr·kg, respectively. The absolute bioavailabilities after IM route were 45.96% (forelimb) and 52.09% (hindlimb). The lack of statistically significant differences in most of the pharmacokinetic parameters after the two IM injection sites suggests a negligible influence of renal portal system in clinical use of MBX, although the Cmax after IMfore administration is advantageous, having into account the concentration-dependent action of this antibiotic. The absence of visible adverse reactions in the animals and the advantageous pharmacokinetic properties suggest the possibility of its safe and effective clinical use in red-eared sliders.  相似文献   

13.
The disposition kinetics of moxifloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration was determined in sheep at a single dose of 5 mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental (after IV, IM and SC administration) pharmacokinetic methods. Plasma concentrations of moxifloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (Vss) and clearance (Cl) of moxifloxacin after IV administration were 2.03 ± 0.36 L/kg and 0.39 ± 0.04 L/h kg, respectively. Following IM and SC administration, moxifloxacin achieved maximum plasma concentration of 1.66 ± 0.62 mg/L and 0.90 ± 0.19 mg/L at 2.25 ± 0.88 h and 3.25 ± 1.17 h, respectively. The absolute bioavailabilities after IM and SC routes were 96.12 ± 32.70% and 102.20 ± 23.76%, respectively. From these data (kinetic parameters and absence of adverse reactions) moxifloxacin may be a potentially useful antibiotic in sheep.  相似文献   

14.
The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (Tmax) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.  相似文献   

15.
The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4 kg. Each dog received either intravenous or subcutaneous injection, both at 5 mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t1/2λz) was calculated as 7.40 ± 0.79 and 7.91 ± 1.53 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (VSS) were determined as 39.91 ± 4.04 ml hr−1 kg−1 and 345.71 ± 28.66 ml/kg, respectively. After subcutaneous injection, the peak concentration (Cmax; 10.50 ± 0.22 μg/ml) was observed at 3.2 ± 1.1 hr, and the absorption half-life (t1/2ka) and absolute bioavailability (F) were calculated as 0.74 ± 0.23 hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T > MIC) values calculated here, an intravenous or subcutaneous dose at 5 mg/kg of ceftiofur sodium once every 12 hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0 μg/ml.  相似文献   

16.
The study was carried out to evaluate the pharmacokinetic disposition of enrofloxacin (ENF) with a single dose of 20 mg/kg after oral administration in largemouth bass (Micropterus salmoides) at 28°C. The concentrations of ENF and of its metabolite ciprofloxacin (CIP) in plasma, liver, and muscle plus skin in natural proportions were determined using HPLC. The concentration–time data for ENF in plasma were best described by a two-compartment open model. After oral administration, the maximum ENF concentration (Cmax) of 10.99 μg/ml was obtained at 0.60 hr. The absorption half-life (T1/2Ka) of ENF was calculated to be 0.07 hr whereas the elimination half-life (T1/2β) of the drug was 90.79 hr. The estimates of area under the plasma concentration–time curve (AUC) and apparent volume of distribution (Vd/F) were 1,185.73 μg hr/ml and 2.21 L/kg, respectively. ENF residues were slowly depleted from the liver and muscle plus skin of largemouth bass with the T1/2β of 124.73 and 115.14 hr, respectively. Very low levels of ciprofloxacin were detected in the plasma and tissues. A withdrawal time of 24 days was necessary to ensure that the residues of ENF + CIP in muscle plus skin were less than the maximal residue limit (MRL) of 100 μg/kg established by the European Union.  相似文献   

17.
Green sea turtles are widely distributed in tropical and subtropical waters. Adult green sea turtles face many threats, primarily from humans, including injuries from boat propellers, being caught in fishing nets, pollution, poaching, and infectious diseases. To the best of our knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for green sea turtles. Therefore, the present study aimed to describe the pharmacokinetic characteristics of ceftriaxone (CEF) in green sea turtles, Chelonia mydas, following single intravenous and intramuscular administrations at two dosages of 10 and 25 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 96 hr. The plasma concentrations of CEF were measured by liquid chromatography tandem mass spectrometry. The concentrations of CEF in the plasma were quantified up to 24 and 48 hr after i.v. and i.m. administrations at dosages of 10 and 25 mg/kg b.w., respectively. The Cmax values of CEF were 15.43 ± 3.71 μg/ml and 43.48 ± 4.29 μg/ml at dosages of 10 and 25 mg/kg, respectively. The AUClast values increased in a dose‐dependent fashion. The half‐life values were 2.89 ± 0.41 hr and 5.96 ± 0.26 hr at dosages of 10 and 25 mg/kg b.w, respectively. The absolute i.m. bioavailability was 67% and 108%, and the binding percentage of CEF to plasma protein was ranged from 20% to 29% with an average of 24.6%. Based on the pharmacokinetic data, susceptibility break‐point and PK‐PD index (T > MIC, 0.2 μg/ml), i.m. administration of CEF at a dosage of 10 mg/kg b.w. might be appropriate for initiating treatment of susceptible bacterial infections in green sea turtles.  相似文献   

18.
Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.  相似文献   

19.
Devil's claw is used for the treatment of inflammatory symptoms and degenerative disorders in horses since many years, but without the substantive pharmacokinetic data. The pharmacokinetic parameters of harpagoside, the main active constituent of Harpagophytum procumbens DC ex Meisn., were evaluated in equine plasma after administration of Harpagophytum extract FB 8858 in an open, single‐dose, two‐treatment, two‐period, randomized cross‐over design. Six horses received a single dose of Harpagophytum extract, corresponding to 5 mg/kg BM harpagoside, and after 7 days washout period, 10 mg/kg BM harpagoside via nasogastric tube. Plasma samples at certain time points (before and 0–24 hr after administration) were collected, cleaned up by solid‐phase extraction, and harpagoside concentrations were determined by LC‐MS/MS using apigenin‐7‐glucoside as internal standard. Plasma concentration‐time data and relevant parameters were described by noncompartmental model through PKSolver software. Harpagoside could be detected up to 9 hr after administration. Cmax was found at 25.59 and 55.46 ng/ml, t1/2 at 2.53 and 2.32 hr, respectively, and tmax at 1 hr in both trials. AUC0–inf was 70.46 and 117.85 ng hr ml?1, respectively. A proportional relationship between dose, Cmax and AUC was observed. Distribution (Vz/F) was 259.04 and 283.83 L/kg and clearance (CL/F) 70.96 and 84.86 L hr?1 kg?1, respectively. Treatment of horses with Harpagophytum extract did not cause any clinically detectable side effects.  相似文献   

20.
Florfenicol, a structural analog of thiamphenicol, has broad‐spectrum antibacterial activity against gram‐negative and gram‐positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic–pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK‐PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC50 (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time‐killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC24 hr, AUC0–∞, Tmax, T1/2, Cmax, CLb, and Ke were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr?1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr?1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.  相似文献   

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