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1.
Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (CS0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC90) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC0-12/MIC90 ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC0-12/MIC90 ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.  相似文献   

2.
Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC50) of field isolates of Escherichia coli. Salmonella and Pasteurella were 0.10–0.40 μg/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half-life of cefixime after intravenous and oral administration was 3.5–4.0 h, the steady-state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 μg/mL for the milk-fed calves and 1.76 μg/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC50 of the drug for gram-negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.  相似文献   

3.
Nine male dogs (10.3–13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC 90 for Escherichia coll (4.0 μg/mL) and Proteus mirabilis (1.0 μg/mL) for over 24 h after doses of 2.2 mg/kg (8.1 μg/mL) and 4.4 mg/kg (29.6 μg/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC 90 for E.coli and P. mirabills (0.6 μg/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 ± 0.0990 μg/mL, 8.91 ± 6.42 μg/mL, and 26.7 ± 1.07 μg/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.  相似文献   

4.
Pharmacokinetics of cefoperazone in horses   总被引：1，自引：0，他引：1  
The pharmacokinetics and bioavailabilty of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase ( t 1/2(α):4.22 ± 2.73 min) was followed by a slower elimination phase ( t 1/2(β) 0.77 ± 0.19 h). The apparent volume of distribution was 0.68 ± 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 ± 0.74 μg/mL. After IM administration a bioavailability of 42.00±5.33% was obtained. Half-life of absorption was 2.51 ± 0.72 min and t 1/2(β) was 1.52±0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91±0.85 μg/mL and 5.56±0.70 μg/mL, respectively.  相似文献   

5.
The pharmacokinetics of sulphadiazine (SDZ) (100 mg/kg, body weight) were investigated in six camels ( Camelus dromedarius ) after intravenous (i.v.) and oral (p.o.) administration. Following i.v. administration, the overall elimination rate constant (β) was 0.029±0.001/h and the half-life ( t ½β) was 23.14±1.06 h. The apparent volume of distribution ( V d(area)) was 0.790±0.075 L/kg and the total body clearance ( Cl B) was 23.29±2.50 mL/h/kg. After p.o. administration, SDZ reached a peak plasma concentration ( C max(cal.)) of 62.93±2.79 μg/mL at a post injection time of ( T max(cal.)) 22.98±0.83 h. The elimination half-life was 19.79±1.22 h, not significantly different from that obtained by the i.v. route. The mean absorption rate constant (Ka) was 0.056±0.002 h−1 and the mean absorption half-life ( t ½Ka) was 12.33±0.37 h. The mean availability ( F ) of sulphadiazine was 88.2±6.2%.
  To achieve and maintain therapeutically satisfactory plasma SDZ levels of 50 μg/mL, the priming and maintenance doses would be 80 mg/kg and 40 mg/kg intravenously and 90 mg/kg and 45 mg/kg orally, respectively, to be repeated at 24 h intervals.  相似文献   

6.
The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC50-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF were collected once during treatment; 1 h after the last administration. This dosage regimen resulted in plasma concentrations that were higher than the EC50-value of 1.7 μg/mL, i.e. EC50 of an isolate highly susceptible to acyclovir, for 80% of the treatment period; and higher than the EC50-value of 3.0 μg/mL, i.e. EC50 of an isolate less susceptible to acyclovir, for 60% of the treatment period. Concentration in nasal mucus samples and CSF was 0.36–1.17 μg/mL and 0.11–0.23 μg/mL, respectively. This study illustrates that multiple dosing of valacyclovir may result in a therapeutic benefit as plasma concentrations could be maintained above the EC50-value of acyclovir against EHV1 for more than 50% of the treatment period. Acyclovir could be detected in both nasal mucus samples and CSF. However, these concentrations were lower than the EC50.  相似文献   

7.
Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations ( C max) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The C max in milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular administration.  相似文献   

8.
The aim of this study was to determine the in vitro antifungal activity of several antifungal drugs (posaconazole, nystatin, miconazole and clotrimazole) against Malassezia pachydermatis with microdilution and agar dilution techniques. Malassezia pachydermatis isolates were obtained from the skin and ears of dogs. Tests on solid media were performed using 25-well Petri dishes (2 mL/well containing Sabouraud's dextrose agar and diluted antifungal drug) inoculated with 5 μL suspensions of M. pachydermatis . Microtitre broth dilution used 96-well microtitre plates containing Sabourauds dextrose broth and appropriate dilutions of antifungal drugs, inoculated with 10 μL standard suspensions of M. pachydermatis . Plates were inoculated in duplicate and incubated at 30°C for 5 days and growth assessed. The four antifungal drugs were tested in 10 dilutions (4.0-0.007 μg/mL for posaconazole, and 32--0.06 μg/mL for clotrimazole, miconazole and nystatin). Results obtained for 83 strains of M. pachydermatis and a control reference strain (CBS 1879) exhibited the same pattern. Results of the MIC between microtitre and agar methodologies showed no significant differences (≤ 2-fold) across all drugs. For both solid and liquid methods, posaconazole was the most effective antifungal drug of the four tested with MIC90 of 1–2 μg/mL for posaconazole, 16–32 μg/mL for clotrimazole, and ≥ 32 μg/mL for miconazole and nystatin.
Funding: Schering-Plough.  相似文献   

9.
The pharmacokinetics of oxolinic acid was studied in sea-bass ( Dicentrarchus labrax ). The fish were kept in seawater at 15.2°C with a 12 h/12 h photoperiod. Oxolinic acid was injected in the caudal vein of anaesthetized sea-bass in a single rapid intravascular administration at a dose of 10 mg/kg of body weight. Plasma concentrations of oxolinic acid were determined using two analytical methods, a classic plate diffusion bioassay using Escherichia coli and a high performance liquid chromatography (HPLC) using solid phase extraction with an internal standard and a U.V. detection. The mean recoveries were 99.6% and 110.8% and determination limits were 0.04 μg/mL and 0.02 μg/mL, for the bioassay and the HPLC respectively. Compared to other fish species, the oxolinic acid was rapidly (absorption half life, ta1/2= 0.69 h) distributed to body tissues outside the blood volume (volume of central compartment, Vc= 0.4 L/kg) and presented a large volume of distribution (Vdss= 2.55 L/kg). Considering its disappearance from the central compartment (rate constant: central-eliminated, k 10= 0.16 h–1) and its total body clearance ( Cl t= 0.066 L/kg.h), the elimination phase of the oxolinic acid in sea-bass was shorter than in trout kept in freshwater, and longer than in salmon in seawater. Consequently, the area under the concentration–time curve ( AUC = 157 μg.h/mL) and the mean residence time ( MRT = 42 h) were relatively low and short, respectively.  相似文献   

10.
Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F1α were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2± 1.4 and 7.8± 4.3 μg/mL, respectively. The half-life of elimination ( t ½β) of pentoxifylline was 1.44 h and volume of distribution ( V darea) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F1α increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F1α and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.  相似文献   

11.
The pharmacokinetic properties of pradofloxacin and doxycycline were investigated in serum, saliva, and tear fluid of cats. In a crossover study design, six cats were treated orally with a single dose of pradofloxacin (Veraflox® Oral Suspension 2.5%) and doxycycline (Ronaxan® 100 mg) at 5 mg/kg body weight. Following administration, samples of serum, saliva, and tear fluid were taken in regular intervals over a period of 24 h and analysed by turbulent flow chromatography/tandem mass spectrometry. All values are given as mean ± SD. Pradofloxacin reached a mean maximum serum concentration ( C max) of 1.1 ± 0.5 μg/mL after 1.8 ± 1.3 h ( t max). In saliva and tear fluid, mean C max was 6.3 ± 7.0 and 13.4 ± 20.9 μg/mL, respectively, and mean t max was 0.5 ± 0 and 0.8 ± 0.3 h, respectively. Doxycycline reached a mean C max in serum of 4.0 ± 0.8 μg/mL after 4.3 ± 3.2 h. Whilst only at two time-points doxycycline concentrations close to the limit of quantification were determined in tear fluid, no detectable levels were found in saliva. The high concentrations of pradofloxacin in saliva and tear fluid are promising to apply pradofloxacin for the treatment of conjunctivitis and upper respiratory tract infections in cats. As doxycycline is barely secreted into these fluids after oral application the mechanisms of its clinical efficacy remain unclear.  相似文献   

12.
Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap. 11 , 45–49.
Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a Cmax= 0.61 ± 0.15 μg/ml, a T max= 6 h and a t ½= 4.7 ± 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values Cmax= 1.55 ± 0.11 μg/ml, T max= 8 h and 1 max= 4.28 ± 0.18 h were obtained. For the higher dose C max= 3.14 ± 0.04 μg/ml, T max= 8 h and t ½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.  相似文献   

13.
The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a t max of 1.46 ± 0.06 h. The elimination half-life ( t 1/2β) and the mean residence time of norfloxacin in plasma were 4.99 ± 0.28 and 6.05 ± 0.22 h, respectively, after i.m. administration and 3.65 ± 0.16 and 3.34 ± 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 ± 4.4%. Plasma concentrations greater than 0.2 μg/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 ± 0.03 μg/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases ( t 1/2α, t 1/2β) and apparent volume of distribution (Vd(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacln and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 μg/g on day 12 after the end of dosing.  相似文献   

14.
Intravenous (IV) levetiracetam (LEV) is available for humans for bridge therapy when the oral route is unavailable. We investigated the safety and pharmacokinetics of LEV administered intramuscularly (IM), IV, and orally to dogs.
Six Hound dogs received 19.5–22.6 mg/kg of LEV IM, IV and orally with a wash-out period in between. All dogs received 500 mg LEV orally and 5 mL of 100 mg/mL LEV IM. Three dogs received 500 mg of LEV IV and three dogs received 250 mg LEV IV with 250 mg given perivascularly to approximate extravasation. Safety was assessed using a pain scale at time of IM administration and histopathological examination 24 h to 5 days after injection.
Intravenous LEV half-life was 180 ± 18 min. Bioavailability of IM LEV was 100%. Mean time to Tmax after IM was 40 ± 16 min. The mean Cmax IM was 30.3 ± 3 μg/mL compared to the C0 of 37 ± 5 μg/mL for IV. Mean inflammation score (0–4 scale) for IM LEV was 0.28 and for saline 0.62. Extravasation did not cause tissue damage.
Parenteral LEV is well tolerated and appears safe following IM and IV injections in dogs. Parenteral LEV should be evaluated for use in dogs with epilepsy.  相似文献   

15.
Sodium meclofenamate is a non-steroidal anti-inflammatory drug with anaphylactic protective activity in cattle. The objectives of this study were to describe the pharmacokinetic behaviour of sodium meclofenamate after intravenous and oral administration to sheep and to determine the influence of closure of the reticular groove on the bioavailability of the drug. Sodium meclofenamate was administered by the intravenous (2.2 mg/kg) and oral (20 mg/kg) routes to sheep (n = 6). During the oral study the reticular groove was closed by intravenous administration of lysine vasopressin (0.3 IU/kg) or left open (saline solution). The closure of the reticular groove was assessed by determination of the blood glucose curves after oral administration of a glucose solution. After intravenous administration of meclofenamate, the distribution and elimination half-lives of the drug were 7.2 min and 542 min respectively, Vss was 1.68 L/kg and ClB was 2.47 mL/min kg. Two different patterns of the plasma concentration curves were observed after oral administration of sodium meclofenamate. When the reticular groove was closed, two peaks were observed ( t max-2 12-15 min, C max-1 3.30-24.01 μg/mL; and t max-2', 52.50-75 min, C max-2' 6.45-11.08 μg/mL).  相似文献   

16.
The purpose of the study was to compare the pharmacokinetics of amikacin administered i.v., to Greyhound and Beagle dogs and determine amikacin pharmacokinetics administered subcutaneously to Greyhounds. Amikacin was administered i.v. at 10 mg/kg to six healthy Greyhounds and six healthy Beagles. The Greyhounds also received amikacin, 10 mg/kg s.c. Plasma was sampled at predetermined time points and amikacin concentrations determined by a fluorescence polarization immunoassay (FPIA).
The volume of distribution was significantly smaller in Greyhounds (mean = 176.5 mL/kg) compared to Beagles (234.0 mL/kg). The C 0 and AUC were significantly larger in Greyhounds (86.03 μg/mL and 79.97 h·μg/mL) compared to Beagles (69.97 μg/mL and 50.04 h·μg/mL). The plasma clearance was significantly lower in Greyhounds (2.08 mL/min/kg) compared to Beagles (3.33 mL/min/kg). The fraction of the dose absorbed after s.c. administration to Greyhounds was 0.91, the mean absorption time was 0.87 h, and the mean maximum plasma concentration was 27.40 μg/mL at 0.64 h.
Significant differences in the pharmacokinetics of amikacin in Greyhounds indicate it should be administered at a lower dose compared to Beagles. The dose in Greyhounds to achieve a C max: AUC  ≥ 8 for bacteria (with an MIC  ≤ 4 μg/mL) is 12 mg/kg q24 h compared to 22 mg/kg q24 in Beagles.  相似文献   

17.
The effects of metaraminol bitartrate on intraocular pressure (IOP) were studied in dogs anesthetized with halothane. Forty-five healthy, adult, mixed-breed dogs, of both sexes, were divided into three groups of 15 dogs each (GI, GII and GIII) and maintained under general anesthesia with halothane after tranquilization with levomepromazine and induction with thiopental. Saline (0.9%) was administered intravenously (IV) to GI through continuous infusion, at a velocity of 0.125 mL kg−1 min−1. GII and GIII received metaraminol 0.004% IV, at a dose of 5 μg kg−1 min−1, at 0.125 mL kg−1 min−1 and at a dose of 2 μg kg−1 min−1, at 0.06 mL kg−1 min−1, respectively. IOP was measured by applanation tonometry (Tono-Pen) before and during anesthesia. Results showed that IOP decreased in GI, increased in GII, and remained at basal levels in GIII. Continuous infusion of metaraminol at 2 μg kg min−1 maintained IOP at pretest levels, while infusion at 5 μg kg−1 min−1 produced an elevation of IOP.  相似文献   

18.
The in vitro sensitivity of 592 Gram-negative bacteria isolated from cattle against polymyxin B was determined by the agar plate dilution method. The minimal inhibitory concentration of polymyxin B for all but ten of the isolates was ≤ 2.0 μg/ml and 75% of the isolates were inhibited at 1.0 μg of polymyxin B/ml or less. Intramuscular injections of polymyxin B, colistin and colistimethate (CMS) were given to veal calves once daily for 3 days. Mean peak serum drug concentrations were observed within 0.5–1 h after treatment and were between 2.7 and 4.7 μg/ml when polymyxin B and colistin were administered at a dose rate of 2.5 mg/kg/day, and between 5.3 and 7.5 μg/ml at dose rate of 5.0 mg/kg/day. When CMS was given at 5.0 mg/kg/day mean peak drug concentration was 14.1 μg/ml. The elimination half-life ( t 1/2) of polymyxin B and colistin was 4–5 h but was approximately 2 h for CMS. Kidney function tests, using the double isotope single-injection method, were performed before and after the course of antibiotic treatment. No changes were detected in the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF) and blood urea levels were not raised following treatment. Several calves treated with the higher doses of polymyxin B and colistin exhibited transient ataxia and apathy 2–4 h after treatment but clinical signs suggesting interference with neurological function were not observed after an equivalent dose of CMS was administered.  相似文献   

19.
Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half-life ( t 1/2β) after the intravenous injection was 4.2 ± 0.5 h, the volume of distribution ( V d(ss)) 1.1±0.2 L/kg and the total body clearance ( Cl B) 131.2 ± 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 ± 16%. The plasma maximum concentration ( C max) 31.9 ± 2.3 μg/mL was reached 2 h after the oral administration and the oral elimination half-life ( t 1/2β) was 4.7 ± 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [3H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1-4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/kg metronidazole.  相似文献   

20.
Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration ( C max), and areas under the concentration curve ( AUC0– ) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC0– of 457 ± 66 ng±day/mL (± SD) and a mean C max of 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC 0– of 475 ± 82 ng-day/mL and a mean C max of 33.1 ± 9.0 ng/mL Absorption constants ( k a) determined by modelling were 0.542 ± 0.336 day-1after sc administration and 0.710 ± 0.357 day-1after i.m. administration. The 90% confidence limits on the difference between mean AUC 0– values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. C max was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In ( T max+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.  相似文献   

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