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1.
OBJECTIVE: To determine the effects of SC administration of filgrastim on cell counts in venous blood and bone marrow of healthy adult alpacas. ANIMALS: 10 healthy alpacas. PROCEDURES: Alpacas were randomly assigned to receive treatment with filgrastim (5 microg/kg, SC; n=5) or an equivalent volume of physiologic saline (0.9% NaCl) solution (5) once a day for 3 days. Blood samples were obtained via jugular venipuncture 1 day prior to treatment and once a day for 5 days commencing 24 hours after the first dose was administered. Complete blood counts were performed for each blood sample. Bone marrow aspirates were obtained from the sternum of each alpaca 48 hours before the first treatment was administered and 72 hours after the third treatment was administered. Myeloid-to-erythroid cell (M:E) ratio was determined via cytologic evaluation of bone marrow aspirates. RESULTS: In filgrastim-treated alpacas, substantial increases in counts of WBCs and neutrophils were detected within 24 hours after the first dose was administered. Band cell count and percentage significantly increased 24 hours after the second dose. Counts of WBCs, neutrophils, and band cells remained high 48 hours after the third dose. Red blood cell counts and PCV were unaffected. The M:E ratio also increased significantly after treatment with filgrastim. CONCLUSIONS AND CLINICAL RELEVANCE: Filgrastim induced rapid and substantial increases in numbers of circulating neutrophils and M:E ratios of bone marrow in healthy alpacas. Therefore, filgrastim may be useful in the treatment of camelids with impaired bone marrow function.  相似文献   

2.
To investigate the relationship between duodenogastric reflux and ulceration, gastric fluid was collected from the 1st (n = 26) and 3rd (n = 45) gastric compartments of llamas and alpacas during postmortem examination. Gastric fluids were analyzed for the presence of bile acids. Additionally, the 3rd compartment was examined grossly for the presence of erosions or ulcers, and the intestines were examined for evidence of fluid distention. Detectable bile acids were found in the 3rd compartment fluid of 1 of 28 camelids without ulcers, 7 of 14 camelids with ulcers, and 3 of 3 camelids with intestinal distention. Third compartment bile content was significantly higher in camelids with ulcers (median = 2.9 micromol/L) or intestinal distention (median = 371.5 micromol/L) than those with neither (median = 0 micromol/L). Bile acids were detected in the 1st gastric compartment in only 2 camelids. These findings suggest a reflux of duodenal contents, including bile acids, into the 3rd compartment in camelids with ulcers, similar to what is seen in camelids with poor intestinal emptying. Whether bile reflux was the cause of the ulcers or occurred after or concurrent to their development remains unknown.  相似文献   

3.
OBJECTIVE: To evaluate effects of hydrocortisone administration, with and without concurrent administration of insulin, on intermediary metabolism in alpacas. ANIMALS: 8 adult castrated male alpacas. PROCEDURE: On each of 2 consecutive days, food was withheld from alpacas for 8 hours. Alpacas then were administered 1 mg of hydrocortisone sodium succinate/kg, IV (time 0). On 1 of the days, randomly assigned alpacas were also administered regular insulin (0.2 U/kg, IV) 120 minutes after hydrocortisone administration. Blood samples were collected at 0, 120, 135, 150, 165, 180, 210, 240, 300, and 360 minutes. Plasma concentrations of glucose and lactate and serum concentrations of triglycerides, cholesterol, nonesterified fatty acids, and beta-hydroxybutyrate were determined. Data were compared between days. Additionally, serum insulin concentrations before and after hydrocortisone administration were determined for selected samples. RESULTS: Hydrocortisone administration induced hyperglycemia, hyperinsulinemia, a reduction in concentrations of triglycerides and cholesterol, and a reduction in triglyceride-to-cholesterol ratio. Subsequent insulin administration temporarily negated the hyperglycemic effects of hydrocortisone, induced temporary hyperlactemia, and augmented the reduction in blood triglycerides. CONCLUSIONS AND CLINICAL RELEVANCE: A single dose of a short-acting corticosteroid does not increase blood lipid fractions in healthy alpacas, probably because of a competent endogenous insulin response. Corticosteroids may induce differing responses in camelids with depleted glycogen stores or an ineffective insulin response. Administration of insulin can effectively negate the hyperglycemic effects of hydrocortisone and augment lipoprotein clearance. Hence, insulin administration may be therapeutic for alpacas with hyperglycemia, hyperlipemia, or hyperketonemia.  相似文献   

4.
Background: Exenatide is a degradation-resistant glucagon-like peptide 1 agonist used in the treatment of diabetes mellitus. It enhances the insulin response to hyperglycemia. Because of a poor insulin response, adult camelids are susceptible to hyperglycemia from stress, glucose administration, or energy metabolism disorders. Insulin often is administered to decrease plasma glucose concentration, but this approach has disadvantages such as the risk of hypoglycemia. Noninsulin medications targeting the incretin hormone pathway, such as exenatide, are providing alternate treatment options.
Hypothesis/Objectives: Exenatide will decrease plasma glucose and increase insulin concentrations in alpacas.
Animals: Six healthy adult alpacas.
Methods: After food was withheld for 8 hours, alpacas were given, on subsequent days in a randomly determined order, either 0.2 μg/kg of exenatide or similar volume of isotonic saline SC. Blood samples were collected before and 15, 30, 45, 60, 75, 90, 105, and 120 minutes after treatment. A rapid dextrose (0.5 g/kg) injection was given after the time 60 samples. Plasma glucose and insulin concentrations were measured at each time point.
Results: Alpacas had significantly ( P = < .001–.015) lower plasma glucose and higher insulin concentrations for the hyperglycemic period after receiving exenatide than after saline injections. Colic signs were observed in 5 of 6 alpacas treated with exenatide.
Conclusions and Clinical Importance: Exenatide appeared to increase insulin release and decrease plasma glucose concentrations in hyperglycemic alpacas. These findings are similar to findings in humans and could support therapeutic usage of exenatide in alpacas. However, induction of colic may limit practical application.  相似文献   

5.
ObjectivesTo evaluate the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to alpacas in comparison with intravenously (IV) administered detomidine.Study designRandomized, crossover, blinded experiment.AnimalsA group of six healthy adult female Huacaya alpacas (70.3 ± 7.9 kg).MethodsAlpacas were studied on two occasions separated by ≥5 days. Treatments were IV detomidine hydrochloride (70 μg kg−1; treatment DET–IV) or detomidine gel (200 μg kg−1; treatment DET–VAG) administered intravaginally. Sedation and heart rate (HR) were evaluated at intervals for 240 minutes. Venous blood was collected at intervals for 360 minutes after treatment for analysis of detomidine, carboxydetomidine and hydroxydetomidine using liquid chromatography–tandem mass spectrometry. Measured variables were compared between treatments and over time using mixed model analysis. Data are presented as the mean ± standard error of the mean, and a p value of <0.05 was considered significant.ResultsOnset of sedation was faster in treatment DET–IV (1.6 ± 0.2 minutes) than in treatment DET–VAG (13.0 ± 2.5 minutes). Time to maximum sedation was shorter in treatment DET–IV (8.3 ± 1.3 minutes) than in treatment DET–VAG (25 ± 4 minutes). Duration of sedation was not different between treatments. There was a significant linear relationship between sedation score and plasma detomidine concentration. HR was less than baseline for 60 and 125 minutes for treatments DET–IV and DET–VAG, respectively. The maximal decrease in HR occurred at 15 minutes for both treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment DET–VAG were 39.6 ng mL−1, 19.9 minutes and 20%, respectively.Conclusions and clinical relevanceDetomidine administration at the doses studied resulted in moderate sedation when administered IV or intravaginally to alpacas.  相似文献   

6.
OBJECTIVE: To describe the metabolic effects of epinephrine administration in New World camelids and investigate whether these effects are influenced by administration of insulin. ANIMALS: 6 llamas and 8 alpacas (all adult castrated males). PROCEDURE: Prior to each experiment, food was withheld from camelids for 8 hours. On each of 2 consecutive days, alpacas were administered epinephrine (10 mg/kg, IM; time 0); alpacas were randomly assigned to receive regular insulin (0.2 U/kg, IV) immediately after epinephrine administration on one of those days. In llamas, the experiment was performed once after administration of epinephrine only. At 0, 30, 60, 90, 120, 150, 180, 210, and 240 minutes after treatment, blood samples were collected and several serum or plasma biochemical variables were assessed; in addition, plasma samples from llamas were assessed for insulin concentrations. Data were compared between days (alpacas only) and between time points. RESULTS: Administration of epinephrine induced mobilization of glucose, triglycerides, nonesterified fatty acids, and beta-hydroxybutyrate. A small increase in endogenous insulin concentration was detected in epinephrine-treated llamas, compared with baseline values. Overall, insulin administration decreased, negated, or delayed the epinephrine-associated increases in serum or plasma concentrations of circulating energy substrates, except that it augmented the epinephrine-associated increase in concentration of triglycerides. CONCLUSIONS AND CLINICAL RELEVANCE: Epinephrine appeared to mobilize energy substrates in camelids and hence may be involved in the pathogenesis of disorders of glucose and fat metabolism. Insulin appeared to antagonize most of these effects, and its administration may have therapeutic value in camelids.  相似文献   

7.
OBJECTIVE: To evaluate the effects of long-acting insulin on glucose clearance in alpacas. ANIMALS: 8 adult castrated alpacas. PROCEDURE: On 2 days, food was withheld from alpacas for 8 hours. Alpacas were randomly allocated to receive an SC injection of long-acting insulin (0.4 U/kg) or saline (0.9% NaCI) solution 1 hour before the first of 3 administrations of glucose (at 60, 480, and 1,200 minutes after treatment) on day 1 and the alternate treatment and procedure on day 2. Plasma glucose concentration was determined before and 15, 45, 120, and 240 minutes after each glucose administration, and fractional turnover rates were calculated. The data were compared between alpacas with and without insulin administration and among the 3 glucose administrations for each day. RESULTS: Compared with sham-treated alpacas, insulin-treated alpacas had significantly lower blood glucose concentrations from 180 to 600 minutes after treatment; they also had glucose concentrations significantly below baseline values from 120 to 480 minutes, at which time the mean glucose concentration was in the hypoglycemic range. Also, mean fractional turnover of glucose was significantly higher in insulin-treated alpacas from 105 through 300 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with known effects of regular insulin in alpacas, the action of long-acting insulin was of slower onset but longer lasting; its administration may induce hypoglycemia, even in alpacas that receive glucose. To maintain the hypoglycemic effect, long-acting insulin may have to be administered more than once daily and blood glucose concentration should be monitored to avoid hypoglycemic complications in alpacas.  相似文献   

8.
Objective To develop a simple and effective surgical technique for third‐compartment cannulation in alpacas. Design Prospective study using six adult male alpacas. Methods General anaesthesia was induced and a polyurethane gastrostomy tube was surgically implanted into the distal portion of the third compartment. Results Three of the alpacas retained their cannulas for a 100‐day period; however, three cannulas were dislodged during the study. Two of the three dislodged cannulas were replaced during a second surgical procedure. Cannulas were well tolerated by the alpacas and all animals remained clinically healthy during the study period. Third compartment contents did not leak from the cannulation site. The tubes were manually removed following the completion of the study and the small defect in the body wall quickly healed over in all animals. Conclusion Surgical placement of polyurethane tubes designed for percutaneous endoscopic gastrostomy is a useful method of cannulating the third compartment in camelids. This technique can be used for experimental studies and possibly could be used for nutritional support and fluid therapy in sick camelids that might need long‐term care.  相似文献   

9.
The objective of this research was to evaluate comparative pharmacokinetics of doramectin in alpacas, after subcutaneous administration of 0.2 mg/kg dose. Six healthy adult alpacas, mean age of 5 years ± 1, (three female and three gelded males) of mean bodyweight of 62 kg ± 16 kg with an average body condition scored 2.8 ± 1 out of five, were used in this study. Serial blood samples were collected from the jugular vein before the administration until day 21 afterwards to establish the pharmacokinetics of doramectin after its subcutaneous administration at 0.2 mg/kg dose. The blood samples were analysed using high-performance liquid chromatography (HPLC), fluorescence detection method with precolumn derivatisation, validated for alpacas. The pharmacokinetic parameters were calculated using a noncompartmental model, and results showed Cmax (6.05 ± 5.34 ng/ml), Tmax (3.83 ± 2.48 days), AUC (62.12 ± 18.86 ng/ml × d), terminal half-life (6.2 ± 4.9 days) and MRT (11.56 ± 4.43 days). The results of this study showed that the Cmax and AUC were much lower than in cattle and sheep at the same dosage. Tmax remained similar to cattle and sheep. This study presents valuable information about pharmacokinetics of doramectin in alpacas, which can be utilised in its future efficacy studies.  相似文献   

10.
The study objective was to evaluate the effects of age on aminoglycoside pharmacokinetics in eight young‐adult (<4 years) and eight aged (≥14 years) healthy alpacas, receiving a single 6.6 mg/kg intravenous gentamicin injection. Heparinized plasma samples were obtained at designated time points following drug administration and frozen at ?80°C until assayed by a validated immunoassay (QMS ®). Compartmental and noncompartmental analyses of gentamicin plasma concentrations versus time were performed using WinNonlin (v6.4) software. Baseline physical and hematological parameters were not significantly different between young and old animals with the exception of sex. Data were best fitted to a two‐compartment pharmacokinetic model. The peak drug concentration at 30 min after dosing (23.8 ± 2.1 vs. 26.1 ± 2 μg/ml, p = .043 ) and area under the curve (70.4 ± 10.5 vs. 90.4 ± 17.6 μg hr/ml, p = .015 ) were significantly lower in young‐adult compared to aged alpacas. Accordingly, young alpacas had a significantly greater systemic clearance than older animals (95.5 ± 14.4 and 75.6 ± 16.1 ml hr?1 kg?1; p = .018 ), respectively). In conclusion, a single 6.6 mg/kg intravenous gentamicin injection achieves target blood concentrations of >10 times the MIC of gentamicin‐susceptible pathogens with MIC levels ≤2 μg/ml, in both young‐adult and geriatric alpacas. However, the observed reduction in gentamicin clearance in aged alpacas may increase their risk for gentamicin‐related adverse drug reactions.  相似文献   

11.
OBJECTIVE: To evaluate the effects of exogenous insulin on clearance of exogenous glucose in alpacas. ANIMALS: 7 adult castrated male alpacas. PROCEDURE: Prior to each of 2 trials, food was withheld for 8 hours. Glucose (0.5 g/kg of body weight) was then administered by rapid IV infusion. During 1 of the trials, regular insulin (0.2 U/kg, IV) was also administered 15 minutes later. Blood was collected immediately before (0 minutes) and 15, 20, 25, 30, 45, 60, 90, 120, 180, and 240 minutes after glucose administration. Plasma concentrations of glucose and lactate were determined, and glucose fractional turnover rate and plasma half-life were calculated. RESULTS: Insulin treatment caused a significant increase in fractional turnover rate of glucose and plasma lactate concentration. Plasma glucose concentrations were less in insulin-treated alpacas from 30 minutes after glucose administration (15 minutes after insulin administration) until the conclusion of each trial, compared with nontreated alpacas. In addition, plasma glucose concentration in insulin-treated alpacas returned to baseline values 1 hour sooner than in the nontreated group. CONCLUSIONS AND CLINICAL RELEVANCE: Glucose uptake in alpacas improves after insulin treatment, suggesting that administration of exogenous insulin will increase the therapeutic and decrease the pathologic effects of exogenous glucose administered to hypoglycemic alpacas. However, alpacas and other New World camelids should be monitored carefully during treatment with glucose or insulin, because these species appear to be partially insulin resistant.  相似文献   

12.
OBJECTIVE: To determine blood glucose clearance in 2 species of New World camelids after IV challenge and to examine mechanisms of this clearance. ANIMALS: 5 adult female llamas and 5 adult gelded alpacas. PROCEDURE: After food was withheld for 12 hours, camelids received 0.5 g of glucose/kg of body weight by rapid IV infusion. Serum concentrations of glucose, nonesterified fatty acids, cortisol, and insulin, and plasma concentrations of lactate were determined before and 0, 1, 2, 3, 4, 5, 15, 30, 60, 90, 120, 180, and 240 minutes after infusion. Ratios of insulin to glucose and insulin to cortisol were calculated for each time point. RESULTS: Postinfusion glucose concentrations were significantly higher in llamas than alpacas for the first 15 minutes and remained significantly higher than baseline values in both species for 180 minutes. Lactate and cortisol concentrations did not change significantly; nonesterified fatty acid concentrations decreased in both species 30 minutes after infusion. Baseline insulin concentrations were < 6 microU/ml in both species and increased only to 10.1 +/- 0.7 microU/ml in llamas. Insulin concentrations did not change significantly in alpacas. CONCLUSIONS AND CLINICAL RELEVANCE: Llamas and alpacas clear glucose more slowly than other domestic species after challenge, mainly because of a weak insulin response and slow cellular uptake. This response may impair the assimilation of exogenous glucose as well as make llamas and alpacas prone to diabetes-like disorders when an abundance of endogenous or exogenous glucogenic agents are present.  相似文献   

13.
Pharmacokinetic studies of antibiotics in South American camelids are uncommon, therefore drugs are often administered to llamas and alpacas based on dosages established in other domestic species. The disposition of ceftiofur sodium was studied in llamas following intramuscular administration and in alpacas following intravenous and intramuscular administration. Eleven adult llamas were given ceftiofur sodium by intramuscular injection. Each animal received either a standard dose of 2.2 mg/kg or an allometrically scaled dose ranging from 2.62 to 2.99 mg/kg in a crossover design. Ten adult alpacas were given ceftiofur sodium by intravenous and intramuscular injections. Each animal received a standard dosage of 1 mg/kg or an allometrically scaled dose ranging from 1.27 to 1.44 mg/kg i.v., and 1.31-1.51 mg/kg i.m. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, and 72 h after administration of the ceftiofur. Pharmacokinetic parameters of ceftiofur in llamas and alpacas were similar following i.m. dosing at both dose levels. The only differences noted were in the total AUC between dose levels, but the AUC/dose values were not different. A sequence effect was noted in the alpaca data, which resulted in lower AUCs for the second dose when the i.v. dose was given first, and with higher AUCs for the second dose when the i.m. dose was given first. Overall, ceftiofur pharmacokinetics in llamas and alpacas are similar, and also very similar to reported parameters for sheep and goats.  相似文献   

14.
REASONS FOR PERFORMING STUDY: Proton pump inhibitors (PPIs) are a mainstay of treatment for acid-related ulceration in man and horses. Currently, only an oral preparation of omeprazole is approved for use in horses in the USA. Intravenous administration of a PPI would provide a useful therapeutic alternative for those foals in which oral medication is not feasible. OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of pantoprazole following i.v. or intragastric administration in healthy neonatal foals. METHODS: Seven healthy foals age 6-12 days at the start of the study were evaluated. Treatments included no drug administration, i.v. pantoprazole (1.5 mg/kg bwt) and intragastric pantoprazole (1.5 mg/kg bwt). Intragastric pH was recorded for 24 h after drug administration for pharmacodynamic evaluation. Plasma pantoprazole concentrations were measured using high-performance liquid chromatography. RESULTS: Plasma concentrations of pantoprazole were detectable at the 5 min sampling point following i.v. or intragastric administration. Bioavailability of intragastric-administered pantoprazole was 41%. Baseline mean hourly pH was 1.5-6.1. There was a statistically significant increase in mean hourly pH relative to untreated foals 2-24 h after i.v. or intragastric pantoprazole administration. CONCLUSIONS: Based on these data, i.v. or intragastric administration of pantoprazole results in a significant, prolonged increase in intragastric pH. POTENTIAL RELEVANCE: The i.v. formulation of pantoprazole may provide a clinically useful alternative means of acid suppression in foals unable to tolerate enteral administration of a PPI, such as those with pyloric outflow obstruction.  相似文献   

15.
OBJECTIVE: To identify the normal gastric acid secretion profile in dogs and determine the degree of gastric acid suppression associated with 4 gastric acid suppressants. ANIMALS: 12 healthy Beagles. PROCEDURE: Intragastric pH was measured continuously for 24-hour periods with a digital recording system placed via a gastrostomy tube. Baseline measurements were obtained when food was withheld and when dogs were fed a standard diet. Dogs were then treated with ranitidine (2 mg/kg, IV, q 12 h), famotidine (0.5 mg/kg, IV, q 12 h), pantoprazole (1 mg/kg, IV, q 24 h), omeprazole (1 mg/kg, PO, q 24 h), or saline solution for 7 days; intragastric pH was recorded on days 0, 2, and 6. Subsequently, the effects of administering famotidine (0.5 mg/kg, IV, q 8 h; 6 dogs) and omeprazole as a suspension (1 mg/kg, PO, q 12 h; 6 dogs) were evaluated. Median 24-hour intragastric pH, percentage of time pH was > or = 3, and percentage of time pH was > or = 4 were determined. RESULTS: Median pH, percentage of time pH was > or = 3, and percentage of time pH was > or = 4 were all significantly higher when food was withheld than when dogs were fed. Famotidine, pantoprazole, and omeprazole significantly suppressed gastric acid secretion, compared with saline solution, as determined on the basis of median 24-hour pH and percentages of time pH was > or = 3 or > or = 4. However, ranitidine did not. Omeprazole suspension suppressed gastric acid secretion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in healthy dogs, famotidine, pantoprazole, and omeprazole significantly suppress gastric acid secretion. Twice daily administration of a suspension of omeprazole, was the only regimen tested that approached the potential therapeutic efficacy for acid-related disease when assessed by criteria used for human patients.  相似文献   

16.
The purpose of the study was to assess the pharmacokinetics of liposome‐encapsulated (DPPC‐C) hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs. A total of eight healthy Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg were used. Dogs randomly received liposome encapsulated hydromorphone, 0.5 mg/kg IV (n = 6), 1.0 mg/kg (n = 6), 2.0 mg/kg (n = 6), or 3.0 mg/kg (n = 7) SC with a 14–28 day washout between trials. Blood was sampled at serial intervals after drug administration. Serum hydromorphone concentrations were measured using liquid chromatography with mass spectrometry. Serum concentrations of hydromorphone decreased rapidly after IV administration of the DPPC‐C formulation (half‐life = 0.52 h, volume of distribution = 12.47 L/kg, serum clearance = 128.97 mL/min/kg). The half‐life of hydromorphone after SC administration of DPPC‐C formulation at 1.0, 2.0, and 3.0 mg/kg was 5.22, 31.48, and 24.05 h, respectively. The maximum serum concentration normalized for dose (CMAX/D) ranged between 19.41–24.96 ng/mL occurring at 0.18–0.27 h. Serum hydromorphone concentrations fluctuated around 4.0 ng/mL from 6–72 h after 2.0 mg/kg and mean concentrations remained above 4 ng/mL for 96 h after 3.0 mg/kg DPPC‐C hydromorphone. Liposome‐encapsulated hydromorphone (DPPC‐C) administered SC to healthy dogs provided a sustained duration of serum hydromorphone concentrations.  相似文献   

17.
The pharmacokinetics of moxifloxacin was studied following intravenous (IV) and subcutaneous (SC) administration of 5 mg/kg to healthy lactating goats (n = 6). Moxifloxacin concentrations were determined by high performance liquid chromatography assay with fluorescence detection. The moxifloxacin plasma concentration versus time data after IV administration could best be described by a two compartment open model. The disposition of SC administered moxifloxacin was best described by a one-compartment model. The plasma moxifloxacin clearance (Cl) for the IV route was 0.43 +/- 0.02 L/kg (mean +/- SE). The steady-state volume of distribution (Vss) was 0.79 +/- 0.08 L/kg. The terminal half-life (t1/2lambdaz) was 1.94 +/- 0.41 and 2.98 +/- 0.48 h after IV and SC administration, respectively. The absolute bioavailability was 96.87 +/- 10.27% after SC administration. Moxifloxacin penetration from blood to milk was quick for both routes of administration and the high AUCmilk/AUCplasma and Cmax-milk/Cmax-plasma ratios reached indicated a wide penetration of moxifloxacin into the milk. From these data, it appears that a 5 mg/kg SC dose of moxifloxacin would be effective in lactating goats against bacterial isolates with MIC < or = 0.20 microg/mL in plasma and MIC < or = 0.40 microg/mL in milk.  相似文献   

18.
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   

19.
Summary

The intravenous and oral pharmacokinetics of an amoxicillin and clavulanic acid combination (20 mg/kg of sodium amoxicillin and 5 mg/kg of potassium clavulanate) were studied in six goats. After intravenous administration the pharmacokinetics of both drugs could be described by an open two‐compartment model. Amoxicillin had a greater distribution volume (0.19 ± 0.01 l/kg) than clavulanic acid (0.15 ± 0.01 l/kg), whereas the distribution and elimination constants were higher for the latter, which was eliminated more quickly than amoxicillin. After oral administration of both drugs their pharmacokinetic behaviour was best described by an open one‐compartment model with first‐order absorption. Elimination half‐lives were twice as long after oral (2.15 ± 0.20 h and 1.94 ± 0.16 h for amoxicillin and clavulanic acid respectively) than after intravenous administration (1.20 ± 0.16 h and 0.86 ± 0.09, respectively). An apparent ‘flip‐flop’ situation was evident in this study. Bioavailability was 27% for amoxicillin and 50% for clavulanic acid.  相似文献   

20.
The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra‐articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3‐way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half‐life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (Cmax) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0–2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on Cmax:MIC of 10.  相似文献   

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