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1.
Romifidine (STH 2130-Cl or Sedivet) is an 2-agonistic imino-imidazol sedative for intravenous use in horses recently developed by Boehringer Ingelheim, Vetmedica GmbH. An exploratory study was done in nine warm-blood horses, randomly divided into three groups, which received different dosages of romifidine (0.04, 0.08 and 0.12 mg/kg of body weight (BWT) intravenously (i.v.)) with at least one week's interval between tests.Romifidine induced a marked bradycardia accompanied by second degree atrioventricular (AV) block and some sinus blocks at all tested dosages. A placebo (NaCl 0.9% i.v.) given 5 min before and after romifidine did not affect the cardiac disturbances induced by romifidine.A low dose of atropine sulphate (0.005 mg/kg of BWT i.v.) given 5 min before romidifine counteracted the bradycardia and caused a normal to increased heart rhythm at all romifidine dosages. A higher dose of atropine sulphate (0.01 mg/kg of BWT i.v.) administered 5 min before sedation induced a tachycardia (average 70 beats/min) at all romifidine dosages and completely prevented the bradycardia and the heart blocks. The positive chronotrope effects of atropine sulphate were attenuated by increasing doses of romifidine.The effects of atropine sulphate (low or high doses) given 5 min after romifidine only appeared after 5 min. Both dosages counteracted the bradycardia and suppressed the heart blocks.No atropine-dependent side effects were observed in non-fasted horses. The degree of the romifidine induced sedation was not affected by the use of atropine sulphate given before or after romifidine.  相似文献   

2.
ObjectiveTo evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration.Study designProspective, experimental, nonrandomized trial.AnimalsA total of 10 healthy adult warmblood horses.MethodsRomifidine (loading dose: 0.08 mg kg–1, infusion: 0.03 mg kg–1 hour–1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic–pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested.ResultsA two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33).Conclusions and clinical relevanceRomifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration.  相似文献   

3.
Terry, R. L., McDonnell, S. M., van Eps, A. W., Soma, L. R., Liu, Y., Uboh, C. E., Moate, P. J., Driessen, B. Pharmacokinetic profile and behavioral effects of gabapentin in the horse. J. vet. Pharmacol. Therap. 33 , 485–494. Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0–48 h postadministration employing liquid chromatography‐tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gabapentin dosage. Nineteen quantitative measures of behaviors were evaluated. After i.v. gabapentin, the decline in plasma drug concentration over time was best described by a 3‐compartment mammillary model. Terminal elimination half‐life (t1/2γ) was 8.5 (7.1–13.3) h. After p.o. gabapentin terminal elimination half‐life () was 7.7 (6.7–11.9) h. The mean oral bioavailability of gabapentin (±SD) was 16.2 ± 2.8% indicating relatively poor absorption of gabapentin following oral administration in horses. Gabapentin caused a significant increase in sedation scores for 1 h after i.v. dose only (P < 0.05). Among behaviors, drinking frequency was greater and standing rest duration was lower with i.v. gabapentin (P < 0.05). Horses tolerated both i.v. and p.o. gabapentin doses well. There were no significant differences in and . Oral administration yielded much lower plasma concentrations because of low bioavailability.  相似文献   

4.
Reasons for performing study: Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. Objectives: To describe the pharmacokinetics of detomidine and its metabolites, 3‐hydroxy‐detomidine (OH‐detomidine) and detomidine 3‐carboxylic acid (COOH‐detomidine), after i.v. and i.m. administration of a single dose to horses. Methods: Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 μg/kg bwt and 4 a single dose i.m. 30 üg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH‐detomidine and COOH‐detomidine were measured at predetermined time points using liquid chromatography‐mass spectrometry. Results: Following i.v. administration, detomidine was distributed rapidly and eliminated with a half‐life (t1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10–18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215–687 ml/kg bwt, respectively. OH‐detomidine was detected sooner than COOH‐detomidine; however, COOH‐detomidine had a much greater area under the curve. Conclusions and potential relevance: These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.  相似文献   

5.
Romifidine is an alpha‐2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low‐dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography–tandem mass spectrometry assay that is currently employed in many drug testing laboratories. An additional objective was to describe changes in heart rate and rhythm following intravenous administration of romifidine followed by exercise. Eight adult Quarter Horses received a single intravenous dose of 5 mg (0.01 mg/kg) romifidine followed by 1 h of exercise. Blood samples were collected and drug concentrations measured at time 0 and at various times up to 72 h. Mean ± SD systemic clearance, steady‐state volume of distribution and terminal elimination half‐life were 34.1 ± 6.06 mL/min/kg and 4.89 ± 1.31 L/kg and 3.09 ± 1.18 h, respectively. Romifidine serum concentrations fell below the LOQ (0.01 ng/mL) and the LOD (0.005 ng/mL) by 24 h postadministration. Heart rate and rhythm appeared unaffected when a low dose of romifidine was administered immediately prior to exercise.  相似文献   

6.
The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high‐performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady‐state volume of distribution (Vss) were 0.15 (0.13–0.18) L hr?1 kg?1 and 1.23 (0.93–1.53) L/kg, respectively. The median (range) elimination half‐life (t1/2) after i.v. and p.o. administration was 7.90 (7.62–8.18) and 12.79 (11.22–16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (Cmax; median: 0.72, range: 0.55–0.93 μg/ml) was achieved in 8 (range 6–12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas.  相似文献   

7.
The behavioural and sedative effects of intravenous (iv) romifidine (40 and 80 μg/kg bodyweight [bwt]) alone or in combination with iv butorphanol (50 μg/kg bwt) were investigated in four ponies and one Thoroughbred horse. Apparent sedation, as judged by the lowering of the head, and by the response to imposed touch, visual and sound stimuli was assessed. The combination with butorphanol reduced the animals' response to imposed stimuli when compared with the effect of the same dose of romifidine alone. Following the administration of romifidine/butorphanol combinations muzzle tremor was noted and some animals attempted to walk forward. In a separate series, the cardiopulmonary effects of iv romifidine (80 μg/kg bwt) alone, or in combination with butorphanol (50 μg/kg bwt) were investigated. Romifidine and the romifidine/butorphanol combination caused similar cardiovascular changes, these being bradycardia with heart block, and hypertension followed by hypotension. Romifidine caused a transient decrease in arterial oxygen tensions and arterial carbon dioxide tensions had increased significantly by the end of the 90 min recording period. Romifidine/butorphanol combinations produced significantly higher arterial carbon dioxide tensions during the first 15 mins after drug administration than did romifidine alone. Butorphanol at 50 μg/kg bwt iv reduced the response to imposed stimuli in horses sedated with romifidine. The combination produced no cardiovascular changes beyond those induced by romifidine alone, but did increase the degree of respiratory depression.  相似文献   

8.
Yamarik, T. A., Wilson, W. D., Wiebe, V. J., Pusterla, N., Edman, J., Papich, M. G. Pharmacokinetics and toxicity of ciprofloxacin in adult horses. J. vet. Pharmacol. Therap. 33 , 587–594. Using a randomized, cross‐over study design, ciprofloxacin was administered i.g. to eight adult mares at a dose of 20 mg/kg, and to seven of the eight horses at a dose of 5 mg/kg by bolus i.v. injection. The mean C0 was 20.5 μg/mL (±8.8) immediately after i.v. administration. The Cmax was 0.6 μg/mL (±0.36) at Tmax 1.46 (±0.66) h after the administration of oral ciprofloxacin. The mean elimination half‐life after i.v. administration was 5.8 (±1.6) h, and after oral administration the terminal half‐life was 3.6 (±1.7) h. The overall mean systemic availability of the oral dose was 10.5 (±2.8)%. Transient adverse effects of mild to moderate severity included agitation, excitement and muscle fasciculation, followed by lethargy, cutaneous edema and loss of appetite developed in all seven horses after i.v. administration. All seven horses developed mild transient diarrhea at 36–48 after i.v. dosing. All eight horses dosed intragastrically experienced adverse events attributable to ciprofloxacin administration. Adverse events included mild transient diarrhea to severe colitis, endotoxemia and laminitis necessitating euthanasia of three horses on humane grounds. The high incidences of adverse events preclude oral and rapid i.v. push administration of ciprofloxacin.  相似文献   

9.
ObjectiveTo determine constant rate infusion (CRI) protocols for romifidine (R) and romifidine combined with butorphanol (RB) resulting in constant sedation and romifidine plasma concentrations.Study designBlinded randomized crossover study.AnimalsTen adult research horses.MethodsPart I: After determining normal height of head above ground (HHAG = 100%), loading doses of romifidine (80 μg kg?1) with butorphanol (RB: 18 μg kg?1) or saline (R) were given intravenously (IV). Immediately afterwards, a butorphanol (RB: 25 μg kg?1 hour?1) or saline (R) CRI was administered for 2 hours. The HHAG was used as marker of sedation depth. Sedation was maintained for 2 hours by additional romifidine (20 μg kg?1) whenever HHAG > 50%. The dose rate of romifidine (μg kg?1 hour?1) required to maintain sedation was calculated for both treatments. Part II: After loading doses, the romifidine CRIs derived from part I were administered in parallel to butorphanol (RB) or saline (R). Sedation and ataxia were evaluated periodically. Romifidine plasma concentrations were measured by HPLC-MS-MS at 0, 5, 10, 15, 30, 45, 60, 90, 105, and 120 minutes. Data were analyzed using paired t-test, Fisher's exact test, Wilcoxon signed rank test, and two-way anova for repeated measures (p < 0.05).ResultsThere was no significant difference in romifidine requirements (R: 30; RB: 29 μg kg?1 hour?1). CRI protocols leading to constant sedation were developed. Time to first additional romifidine bolus was significantly longer in RB (mean ± SD, R: 38.5 ± 13.6; RB: 50.5 ± 11.7 minutes). Constant plasma concentrations of romifidine were achieved during the second hour of CRI. Ataxia was greater when butorphanol was added.ConclusionRomifidine bolus, followed by CRI, provided constant sedation assessed by HHAG. Butorphanol was ineffective in reducing romifidine requirements in unstimulated horses, but prolonged the sedation caused by the initial romifidine bolus.Clinical relevanceBoth protocols need to be tested under clinical conditions.  相似文献   

10.
The disposition of plasma glycopyrrolate (GLY) is characterized by a three‐compartment pharmacokinetic model after a 1‐mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V1), volume of distribution at steady‐state (Vss), and area under the plasma concentration–time curve (AUC0‐inf) were 16.7 (13.6–21.7) mL/min/kg, 0.167 (0.103–0.215) L/kg, 3.69 (0.640–38.73) L/kg, and 2.58 (2.28–2.88) ng*h/mL, respectively. Renal clearance of GLY was characterized by a median (range) of 2.65 (1.92–3.59) mL/min/kg and represented approximately 11.3–24.7% of the total plasma clearance. As a result of these studies, we conclude that the majority of GLY is cleared through hepatic mechanisms because of the limited extent of renal clearance of GLY and absence of plasma esterase activity on GLY metabolism. Although the disposition of GLY after intravenous administration to Standardbred horses was similar to that in Thoroughbred horses, differences in some pharmacokinetic parameter estimates were evident. Such differences could be attributed to breed differences or study conditions. The research could provide valuable data to support regulatory guidelines for GLY in Standardbred horses.  相似文献   

11.
Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap. 34 , 12–16. The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life (t1/2k10) of 12.49 ± 1.84 h. The average maximum plasma concentration (Cmax) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC50 and IC80, respectively. Dosing simulations showed that concentrations above the IC80 for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC50 following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.  相似文献   

12.
Huang, R. A., Letendre, L. T., Banav, N., Fischer, J., Somerville, B. Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity. J. vet. Pharmacol. Therap. 33 , 227–237. The pharmacokinetics (PK) and dose proportionality of gamithromycin (ZACTRAN®), a novel azalide, after a single intravenous (i.v.) dose of 3 mg/kg or subcutaneous (s.c.) injection at 3, 6 and 9 mg/kg body weight were studied in 13 male castrate and 13 female Angus cattle. Following i.v. administration, the mean area under the curve extrapolated to infinity (AUCinf) was 4.28 ± 0.536 μg·h/mL, and mean elimination half‐life (t1/2) was 44.9 ± 4.67 h, with a large volume of distribution (Vss) of 24.9 ± 2.99 L/kg and a high clearance rate (Clobs) of 712 ± 95.7 mL/h/kg. For cattle treated with s.c. injection of 3, 6 or 9 mg/kg, mean AUCinf values were 4.55 ± 0.690, 9.42 ± 1.11 and 12.2 ± 1.13 μg·h/mL, respectively, and the mean elimination half‐lives (t1/2) were 51.2 ± 6.10, 50.8 ± 3.80 and 58.5 ± 5.50 h. Gamithromycin was well absorbed and fully bioavailable (97.6–112%) after s.c. administration. No statistically significant (α = 0.05) gender differences in the AUCInf or elimination half‐life values were observed. Dose proportionality was established based on AUCInf over the range of 0.5 to 1.5 times of the recommended dosage of 6 mg/kg of body weight. Further investigations were conducted to assess plasma PK, lung/plasma concentration ratios and plasma antibacterial activity using 36 cattle. The average maximum gamithromycin concentration measured in whole lung homogenate was 18 500 ng/g at first sampling time of 1 day (～24 h) after treatment. The ratios of lung to plasma concentration were 265, 410, 329 and 247 at 1, 5, 10 and 15 days postdose. The lung AUCinf was 194 times higher than the corresponding plasma AUCinf. The apparent elimination half‐life for gamithromycin in lung was 90.4 h (～4 days). Antibacterial activity was observed with plasma collected at 6 h postdose with a corresponding average gamithromycin plasma concentration of 261 ng/mL. In vitro plasma protein binding in bovine plasma was determined to be 26.0 ± 0.60% bound over a range of 0.1–3.0 μg/mL of gamithromycin. The dose proportionality of AUC, high bioavailability, rapid and extensive distribution to lung tissue and low level of plasma protein binding are beneficial PK parameters for an antimicrobial drug used for the treatment and prevention of bovine respiratory disease.  相似文献   

13.
Collard, W. T., Cox, S. R., Lesman, S. P., Grover, G. S., Boucher, J. F., Hallberg, J. W., Robinson, J. A., Brown, S. A. Pharmacokinetics of ceftiofur crystalline‐free acid sterile suspension in the equine. J. vet. Pharmacol. Therap. 34 , 476–481. Absolute bioavailability and dose proportionality studies were performed with ceftiofur in horses. In the absolute bioavailability study, thirty animals received either an intravenous dose of ceftiofur sodium at 1.0 mg/kg or an intramuscular (i.m.) dose of ceftiofur crystalline‐free acid (CCFA) at 6.6 mg/kg. In the dose proportionality study, 48 animals received daily i.m. ceftiofur sodium injections at 1.0 mg/kg for ten doses or two doses of CCFA separated by 96 h, with CCFA doses of 3.3, 6.6, or 13.2 mg/kg. Noncompartmental and mixed‐effect modeling procedures were used to assess pharmacokinetics (PK). CCFA was well absorbed with a bioavailability of 100%. AUC0–∞ and Cmax increased in a dose‐related manner following administration of the two doses of CCFA at 3.3, 6.6, and 13.2 mg/kg. The least‐squares mean terminal half‐life (t½) following the tenth daily i.m. injection of ceftiofur sodium at 2.2 mg/kg was 40.8 h, but the least‐squares mean t½ following the second i.m. injection of CCFA at 6.6 mg/kg was 100 h. The time that plasma ceftiofur equivalent concentrations remain above a threshold concentration of 0.2 μg/mL has been associated with efficacy, and following administration of two 6.6 mg/kg doses of CCFA, the mean time above 0.2 μg/mL was 262 h. Simulations with the nonlinear mixed‐effect PK model predicted that more than 97.5% of horses will have plasma ceftiofur equivalent concentrations >0.2 μg/mL for 96 h after the second 6.6 mg/kg dose of CCFA.  相似文献   

14.
OBJECTIVE: To investigate the action of a single IV administration of romifidine on the thresholds of the nociceptive withdrawal reflex (NWR) and temporal summation in conscious horses. ANIMALS: 10 adult horses. PROCEDURE: Single electrical stimulations were applied on the digital nerves to evoke NWR from the left forelimb and hind limb. Repeated electrical stimulations (10 stimuli, 5 Hz) were given to obtain temporal summation. Surface electromyographic reflex activity was recorded from the common digital extensor and cranial tibial muscles. After baseline assessment of NWR and temporal summation thresholds, romifidine (80 microg x kg(-1), IV) was administered. Successive determinations of NWR and temporal summation thresholds were performed 5, 25, and 55 minutes after administration. RESULTS: Romifidine significantly increased the current intensities necessary to evoke NWR and temporal summation in forelimbs and hind limbs of horses. Values were significantly higher than baseline values 55 minutes after romifidine administration. After administration of romifidine, a facilitation of reflex components of tactile origin was observed when repeated stimulations were applied. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm antinociceptive activity of romifidine and may represent an objective demonstration of the well-known hypersensitivity to tactile stimuli observed in horses receiving alpha2-adrenoreceptor agonists in clinical practice. Romifidine can be included in analgesic and anesthetic protocols to provide additional analgesia in horses.  相似文献   

15.
Vallé, M., Schneider, M., Galland, D., Giboin, H., Woehrlé, F. Pharmacokinetic and pharmacodynamic testing of marbofloxacin administered as a single injection for the treatment of bovine respiratory disease. J. vet. Pharmacol. Therap. 35, 519–528. New approaches in Pharmacokinetic/Pharmacodynamic (PK/PD) integration suggested that marbofloxacin, a fluoroquinolone already licensed for the treatment of bovine respiratory disease at a daily dosage of 2 mg/kg for 3–5 days, would be equally clinically effective at 10 mg/kg once (Forcyl®), whilst also reducing the risk of resistance. This marbofloxacin dosage regimen was studied using mutant prevention concentration (MPC), PK simulation, PK/PD integration and an in vitro dynamic system. This system simulated the concentration–time profile of marbofloxacin in bovine plasma established in vivo after a single 10 mg/kg intramuscular dose and killing curves of field isolated Pasteurellaceae strains of high (minimum inhibitory concentration (MIC) MIC ≤0.03 μg/mL), average (MIC of 0.12–0.25 μg/mL) and low (MIC of 1 μg/mL) susceptibility to marbofloxacin. The marbofloxacin MPC values were 2‐ to 4‐fold the MIC values for all Mannheimia haemolytica, Pasteurella multocida tested. Marbofloxacin demonstrated a concentration‐dependant killing profile with bactericidal activity observed within 1 h for most strains. No resistance development (MIC ≥4 μg/mL) was detected in the dynamic tests. Target values for risk of resistance PK/PD surrogates (area under the curve (AUC) AUC24 h/MPC and T>MPC/TMSW ratio) were achieved for all clinically susceptible pathogens. The new proposed dosing regimen was validated in vitro and by PK/PD integration confirming the single‐injection short‐acting antibiotic concept.  相似文献   

16.
Lucas, M. F., Errecalde, J. O., Mestorino, N. Pharmacokinetics of azithromycin in lactating dairy cows with subclinical mastitis caused by Staphylococcus aureus. J. vet. Pharmacol. Therap. 33 , 132–140. Azithromycin is a time‐dependent antimicrobial with long persistence. The main characteristics of azithromycin suggest that it could be useful for treating bovine mastitis caused by Staphylococcus aureus. To investigate this possibility, its pharmacokinetic (PK) behavior was studied. Six Holstein lactating cows with subclinical mastitis were administered two 10 mg/kg intramuscular (i.m.) doses of azithromycin, with a 48‐h interval. Milk and plasma concentrations were measured by microbiological assay. The MIC90 was determined in 51 S. aureus isolations to calculate pharmacokinetic/pharmacodynamic (PK/PD) parameters. Milk maximal concentration (Cmax) was 7.76 ± 1.76 μg/mL (16.67 h post‐first administration) and 7.82 ± 2.18 μg/mL (14 h post‐2nd administration). In plasma Cmax was 0.18 ± 0.03 μg/mL (2 h post‐1rst administration) and 0.11 ± 0.03 μg/mL (14 h post‐2nd administration). Azithromycin was eliminated from the milk with a half‐life (T½λ) of 158.26 ± 137.7 h after 2nd administration, meanwhile plasma T½λ resulted shorter(13.97 ± 11.1 h). The mean area under the concentration vs. time curve from 0 to 24 h (AUC0‐24h) was 153.82 ± 34.66 μg·h/mL in milk secretion and 2.61 ± 0.59 μg·h/mL in plasma. Infection presence in the quarters had a significant effect (P < 0.05) on the area under the concentration vs. time curve from 0 to infinity (AUC0‐∞) and clearance from the mammary gland (Clmam/F). Moreover, it had influence on milk bioavailability (Fmilk), T½λ, AUC0‐∞ and mean residence time (MRT) in milk, which values resulted increased in mastitic quarters. In this study, it was determined that the production level and the mammary health status have an influence on PK parameters of azithromycin treatments in bovine mastitis.  相似文献   

17.
Compartmental models were used to investigate the pharmacokinetics of intravenous (i.v. ), oral (p.o. ), and topical (TOP ) administration of dimethyl sulfoxide (DMSO ). The plasma concentration–time curve following a 15‐min i.v. infusion of DMSO was described by a two‐compartment model. Median and range of alpha (t 1/2α) and beta (t 1/2β) half‐lives were 0.029 (0.026–0.093) and 14.1 (6.6–16.4) hr, respectively. Plasma concentration–time curves of DMSO following p.o. and TOP administration were best described by one‐compartment absorption and elimination models. Following the p.o. administration, median absorption (t 1/2ab) and elimination (t 1/2e) half‐lives were 0.15 (0.01–0.77) and 15.5 (8.5–25.2) hr, respectively. The plasma concentrations of DMSO were 47.4–129.9 μg/ml, occurring between 15 min and 4 hr. The fractional absorption (F ) during a 24‐hr period was 47.4 (22.7–98.1)%. Following TOP administrations, the median t 1/2ab and t 1/2e were 1.2 (0.49–2.3) and 4.5 (2.1–11.0) hr, respectively. Plasma concentrations were 1.2–8.2 μg/ml occurring at 2–4 hr. Fractional absorption following TOP administration was 0.48 (0.315–4.4)% of the dose administered. Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2–6.7) ml hr?1 kg?1. The corrected clearances (ClF ) for p.o. and TOP administrations were 2.9 (1.1–5.5) and 4.5 (0.52–18.2) ml hr?1 kg?1.  相似文献   

18.
The pharmacokinetics (PK) of cefquinome (CEQ) was studied in crucian carp (Carassius auratus gibelio) after single oral, intramuscular (i.m.), and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight and following incubation in a 5 mg/L bath for 5 hr at 25°C. The plasma concentration of CEQ was determined using high‐performance liquid chromatography (HPLC). PK parameters were calculated based on mean CEQ concentration using WinNonlin 6.1 software. The disposition of CEQ following oral, i.m., or i.p. administration was best described by a two‐compartment open model with first‐order absorption. After oral, i.m., and i.p. administration, the maximum plasma concentration (Cmax) values were 1.52, 40.53, and 67.87 μg/ml obtained at 0.25, 0.23, and 0.35 hr, respectively, while the elimination half‐life (T1/2β) values were 4.68, 7.39, and 6.88 hr, respectively; the area under the concentration–time curve (AUC) values were 8.61, 339.11, and 495.06 μg hr/ml, respectively. No CEQ was detected in the plasma after bath incubation. Therapeutic blood concentrations of CEQ can be achieved in the crucian carp following i.m. and i.p. administration at a dosage of 10 mg/kg once every 2 days.  相似文献   

19.
OBJECTIVE: To compare detomidine hydrochloride and romifidine as premedicants in horses undergoing elective surgery. ANIMALS: 100 client-owned horses. PROCEDURE: After administration of acepromazine (0.03 mg/kg, IV), 50 horses received detomidine hydrochloride (0.02 mg/kg of body weight, IV) and 50 received romifidine (0.1 mg/kg, IV) before induction and maintenance of anesthesia with ketamine hydrochloride (2 mg/kg) and halothane, respectively. Arterial blood pressure and blood gases, ECG, and heart and respiratory rates were recorded. Induction and recovery were timed and graded. RESULTS: Mean (+/- SD) duration of anesthesia for all horses was 104 +/- 28 minutes. Significant differences in induction and recovery times or grades were not detected between groups. Mean arterial blood pressure (MABP) decreased in both groups 30 minutes after induction, compared with values at 10 minutes. From 40 to 70 minutes after induction, MABP was significantly higher in detomidine-treated horses, compared with romifidine-treated horses, although more romifidine-treated horses received dobutamine infusions. In all horses, mean respiratory rate ranged from 9 to 11 breaths/min, PaO2 from 200 to 300 mm Hg, PaCO2 from 59 to 67 mm Hg, arterial pH from 7.33 to 7.29, and heart rate from 30 to 33 beats/min, with no significant differences between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine and romifidine were both satisfactory premedicants. Romifidine led to more severe hypotension than detomidine, despite administration of dobutamine to more romifidine-treated horses. Both detomidine and romifidine are acceptable alpha2-adrenoceptor agonists for use as premedicants before general anesthesia in horses; however, detomidine may be preferable when maintenance of blood pressure is particularly important.  相似文献   

20.
Objective To determine the electrocardiographic and cardiopulmonary effects of IM administration of romifidine with and without prior administration of glycopyrrolate in conscious dogs. Study design Prospective randomized study. Animals Twelve healthy, adult beagles. Materials and methods Dogs were assigned at random to each of three treatments with glycopyrrolate (six dogs), and to each of three treatments without glycopyrrolate (six dogs). Baseline data were recorded, and saline solution or glycopyrrolate (10 µg kg–1) was given IM. After 15 minutes, saline solution (control) or romifidine (20 or 40 µg kg–1) was given IM. An ECG, heart rate (HR), systemic blood pressures, and respiratory rate (RR) were recorded before and 2.5, 5, 10, 15, 30, 45, 60, 75, 90, 105 and 120 minutes after romifidine administration. Rectal temperature (RT), pH, PaCO2, PaO2, hematocrit and plasma protein were determined before and 15, 30, 60 and 120 minutes after romifidine administration. Data were analyzed using analysis of variance for repeated measures and Tukey multiple comparison tests. Results Without glycopyrrolate, HR (beats minute–1) decreased to minimum values (mean ± SD) of 52 ± 7 and 49 ± 12 (control 89 ± 20) 45 minutes after administration of romifidine at doses of 20 and 40 µg kg–1, respectively. Sinus bradycardia (HR < 60 beats minute–1), which persisted for up to 120 minutes, was observed in five of six and six of six dogs given romifidine at doses of 20 and 40 µg kg–1, respectively. With glycopyrrolate, decreases in HR were prevented and mean arterial pressure (mm Hg) increased to maximum values of 139 ± 25 and 173 ± 17 (control 113 ± 11) 30 minutes after administration of romifidine at doses of 20 and 40 µg kg–1, respectively. With and without glycopyrrolate, RR did not change appreciably, RT decreased, and pH, PaCO2, PaO2, hematocrit and plasma protein did not change after administration of romifidine. Conclusions and clinical relevance In healthy conscious beagles, IM administration of romifidine at doses of 20 and 40 µg kg–1 causes sinus bradycardia which persists for up to 120 minutes. Administration of glycopyrrolate 15 minutes before administration of romifidine, prevents sinus bradycardia and induces moderate increases in arterial pressure.  相似文献   

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