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

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

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Objective

To characterise the minimum dose of intramuscular alfaxalone required to facilitate intubation for mechanical ventilation, and to investigate the impact of cranial versus caudal injection on anaesthetic depth.

Study design

Randomised crossover study.

Animals

Six healthy juvenile ball pythons (Python regius).

Methods

Three dosages (10, 20 and 30 mg kg–1) of alfaxalone were administered to each python in a caudal location with a minimum 2 weeks washout. Induction and recovery were monitored by assessing muscle tone, righting reflex, response to a noxious stimulus and the ability to intubate. A subsequent experiment assessed the influence of injection site by comparing administration of 20 mg kg–1 alfaxalone in a cranial location (1 cm cranial to the heart) with the caudal site. Respiration rate was monitored throughout, and when intubation was possible, snakes were mechanically ventilated.

Results

Regardless of dose and injection site, maximum effect was reached within 10.0 ± 2.7 minutes. When administered at the caudal injection site, intubation was only successful after a dosage of 30 mg kg-1, which is higher than in previous reports for other reptiles. However, intubation was possible in all cases after 7.2 ± 1.6 minutes upon cranial administration of 20 mg kg–1, and anaesthetic duration was significantly lengthened (p < 0.001). Both 30 mg kg–1 at the caudal site and 20 mg kg–1 at the cranial site led to apnoea approximately 10 minutes post-injection, at which time the snakes were intubated and mechanically ventilated.

Conclusions and clinical relevance

Alfaxalone provided rapid, smooth induction when administered intramuscularly to pythons, and may serve as a useful induction agent prior to provision of volatile anaesthetics. The same dosage injected in the cranial site led to deeper anaesthesia than when injected caudally, suggesting that shunting to the liver and first-pass metabolism of alfaxalone occur when injected caudally, via the renal portal system.  相似文献   

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

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AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats.

METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two–treatment, two-period study. Alfaxalone at a dose of 5?mg/kg was administered either I/V or I/M. Blood samples were collected between 2–480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5–120 minutes after drug administration using a numerical rating scale (from 0–18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded.

RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5–15 minutes after I/V administration and deep sedation (scores 11–15) at 20 and 30 minutes. Deep sedation was observed from 10–45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery.

CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.  相似文献   

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Objective

To evaluate the efficacy and side effects of alfaxalone administered intramuscularly (IM) as a sedative agent in guinea pigs undergoing survey radiographs.

Study design

Prospective clinical trial.

Animals

A total of 30 client-owned guinea pigs.

Methods

Following baseline assessments, 5 mg kg?1 alfaxalone was administered IM. Heart rate, arterial haemoglobin oxygen saturation, respiratory rate, rectal body temperature, palpebral reflex, response to toe and ear pinch, righting reflex, posture, jaw tone and reaction to manipulation were assessed before and after sedation at 5-minute intervals. The time elapsed from onset of sedation to return of locomotion and coordinated limb movements, the quality of recovery and the occurrence of undesired effects were observed and recorded.

Results

The mean ± standard deviation onset of sedation was 2.7 ± 0.6 minutes. The physiological variables remained within normal ranges until completion of the procedure. Palpebral reflex and responsiveness to both ear and toe pinch were maintained during sedation. Neither hypoxaemia nor hypothermia was observed. The duration of sedation was 29.3 ± 3.2 minutes. Sedation and recovery were uneventful, and adverse effects were not observed.

Conclusions and clinical relevance

In conclusion, 5 mg kg?1 of IM alfaxalone represents a valuable sedation protocol for healthy guinea pigs undergoing minor noninvasive procedures. Further trials are required to investigate its cardiovascular effects, clinical usefulness in unhealthy patients and its combined use with analgesics for procedures associated with nociception.  相似文献   

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ObjectiveTo document the effects of two doses of dexmedetomidine on the induction characteristics and dose requirements of alfaxalone.Study designRandomized controlled clinical trial.AnimalsSixty one client owned dogs, status ASA I-II.MethodsDogs were allocated randomly into three groups, receiving as pre-anaesthetic medication, no dexmedetomidine (D0), 1 μg kg?1 dexmedetomidine (D1) intramuscularly (IM) or 3 μg kg?1 dexmedetomidine IM (D3). All dogs also received 0.2 mg kg?1 methadone IM. Level of sedation was assessed prior to induction of anaesthesia. Induction of general anaesthesia was performed with alfaxalone administered intravenously to effect at a rate of 1 mg kg?1 minute?1; the required dose to achieve tracheal intubation was recorded. Anaesthesia was maintained with isoflurane in oxygen. Cardiopulmonary parameters were recorded throughout the anaesthetic period. Quality of intubation, induction and recovery of anaesthesia were recorded. Quantitative data were compared with one-way anova or Kruskal-Wallis test. Repeated measures were log-transformed and analysed with repeated measures anova (p < 0.05).ResultsTreatment groups were similar for categorical data, with exception of sedation level (p < 0.001). The doses (mean ± SD) of alfaxalone required for intubation were D0 1.68 ± 0.24, D1 1.60 ± 0.36 and D3 1.41 ± 0.43, the difference between D0 and D3 being statistically significant (p = 0.036). Heart and respiratory rates during the anaesthetic period were significantly different over time and between groups (p < 0.001); systolic arterial blood pressure was significantly different over time (p < 0.001) but not between groups (p = 0.833). Induction quality and recovery scores were similar between groups (p = 1.000 and p = 0.414, respectively).Conclusions and clinical relevanceThe administration of alfaxalone resulted in a good quality anaesthetic induction which was not affected by the dose of dexmedetomidine. Dexmedetomidine at 3 μg kg?1 IM combined with methadone provides good sedation and enables a reduction of alfaxalone requirements.  相似文献   

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Objective

To evaluate the anaesthetic effects of three different alfaxalone doses to induce anaesthesia in goldfish.

Study design

Prospective, randomized, clinical study.

Animals

Thirty goldfish undergoing skin scraping, gill examination and stool collection.

Methods

Each fish was transferred to an individual 4 L induction tank and randomly allocated into one of three groups (n = 10), in which alfaxalone was administered at concentrations of 6, 7 or 9 mg L–1. The depth of anaesthesia was evaluated by approach reaction, equilibrium, opercular movement and reaction to tactile stimuli. Sedation, light anaesthesia, surgical anaesthesia and recovery times were recorded. Data were analyzed with analysis of variance. A p value <0.05 was considered significant.

Results

Surgical anaesthesia was achieved in all fish. Goldfish induced with alfaxalone 7 and 9 mg L–1 showed a mild excitement phase. Time to sedation of the 6 mg L–1 dose (5.89 ± 0.40 minutes) was significantly longer compared to the 7 mg L–1 (3.97 ± 0.40 minutes) and 9 mg L–1 doses (3.94 ± 0.40 minutes). Times to light anaesthesia and surgical anaesthesia of the 9 mg L–1 dose (7.65 ± 1.04 and 9.60 ± 1.84 minutes, respectively) were significantly faster compared with those of the 6 mg L–1 dose (13.79 ± 1.04 and 19.75 ± 1.84 minutes, respectively) and the 7 mg L–1 dose (13.55 ± 1.04 and 21.24 ± 1.84 minutes, respectively). No significant differences were recorded in recovery time. Cessation of opercular movement was recorded in two fish induced with 7 mg L–1 and in two induced with 9 mg L–1. No mortality occurred.

Conclusions

and clinical relevance Alfaxalone is a reliable agent for immersion anaesthesia in goldfish. Immersion in water containing 6 mg alfaxalone L–1 provided smooth induction of anaesthesia, and no obvious side effects were encountered. Higher doses shortened induction time and caused respiratory depression and excitatory movements.  相似文献   

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ObjectiveTo characterise four different intramuscular (IM) anaesthetic protocols, two with alfaxalone and two with alfaxalone in combination with medetomidine in terrestrial tortoises.Study designBlinded, randomized, cross‐over experimental study.AnimalsNine healthy adult male Horsfield's tortoises (Agrionemys horsfieldii).MethodsEach tortoise was randomly assigned to one of four different protocols: 1) 10 mg kg?1 alfaxalone; 2) 10 mg kg?1 alfaxalone + 0.10 mg kg?1 medetomidine; 3) 20 mg kg?1 alfaxalone; and 4) 20 mg kg?1 alfaxalone + 0.05 mg kg?1 medetomidine. During the experiment, the following variables were recorded: heart rate; respiratory rate; peripheral nociceptive responses; muscle strength; ability to intubate; palpebral, corneal and tap reflexes; and cloacal temperature.ResultsProtocols 1 and 2 resulted in moderate sedation with no analgesia, and moderate to deep sedation with minimal analgesia, respectively. Protocols 3 and 4 resulted in deep sedation or anaesthesia with variable analgesic effect; these two protocols had the longest total anaesthetic time and allowed intubation in 6/9 and 8/9 tortoises respectively. The total anaesthesia/sedation time produced by alfaxalone was significantly increased (p <0.05) by the addition of medetomidine. There were no significant differences regarding time to plateau phase and duration of plateau phase. Baseline heart rate of 53 ± 6 beats minute?1 decreased significantly (p <0.05) with all protocols, and was lower (p <0.05) in protocols 3 and 4. Heart rate increased after atipamezole administration, but the increase was transient. In two tortoises, extreme bradycardia with no cardiac activity for 10 minutes was observed with protocols 3 and 4.Conclusion and clinical relevanceAlfaxalone 10 and 20 mg kg?1 IM can be used for sedation for non‐painful procedures. Alfaxalone in combination with medetomidine can be used for deeper sedation or anaesthesia, but the observed respiratory and cardiovascular depression may limit its use.  相似文献   

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ObjectiveTo compare two commercial formulations of alfaxalone for immersion anaesthesia in laboratory zebrafish.Study designProspective, blinded, randomized study.AnimalsA total of 20 adult Danio rerio (Tuebingen strain).MethodsZebrafish were divided into two groups of 10 (five female, five male) and placed in individual immersion baths containing 10 mg L–1 of unpreserved alfaxalone (group 1) or preserved alfaxalone (group 2). Anaesthetists blinded to treatment used a composite score scale (CSS) (range 0–12) to assess fish every 30 seconds until induction of anaesthesia. Anaesthetic induction occurred when equilibrium and response to stimulus were lost. Fish were then placed in a clean water bath and scored every 60 seconds. Recovery from anaesthesia was defined as a CSS of ≤ 1. Time variables recorded were anaesthetic induction time (AIT), anaesthetic recovery time (ART) and total procedure time (TPT). Fish were observed for evidence of roupgross external pathology during the procedure. Following anaesthesia, four fish from each group were randomly chosen and euthanized for gill histopathology analysis immediately after recovery criteria were met. Data are presented as mean ± standard deviation. An independent t test was used to compare the difference in average anaesthetic time variables between groups (α = 0.05).ResultsThere were no statistical differences between groups in reported variables. TPT, AIT and ART were 10.2 ± 1.2, 1.9 ± 0.9 and 8.3 ± 1.2 minutes for group 1 and 10.8 ± 2.9, 2.4 ± 1.2 and 8.4 ± 2.7 minutes for group 2. No gross external pathology was evident, and no fish died during the experimental period. Histopathology showed normal gill pathology and no difference between the groups.Conclusions and clinical relevanceImmersion anaesthesia using 10 mg L–1 of either formulation of alfaxalone resulted in anaesthesia of similar quality and duration.  相似文献   

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Objective

To investigate the clinical and physiological effects of intravenous (IV) alfaxalone alone or in combination with buprenorphine, butorphanol or tramadol premedication in marmosets.

Study design

Prospective, randomized, blinded, crossover design.

Animals

Nine healthy marmosets (391 ± 48 g, 3.7 ± 2.2 years old).

Methods

Meloxicam 0.20 mg kg?1 subcutaneously, atropine 0.05 mg kg?1 intramuscularly (IM) and either buprenorphine 20 μg kg?1 IM (BUP-A), butorphanol 0.2 mg kg?1 IM (BUT-A), tramadol 1.5 mg kg?1 IM (TRA-A) or no additional drug (control) were administered to all marmosets as premedication. After 1 hour, anaesthesia was induced with 16 mg kg?1 alfaxalone IV. All animals received all protocols. The order of protocol allocation was randomized with a minimum 28 day wash-out period. During anaesthesia, respiratory and pulse rates, rectal temperature, haemoglobin oxygen saturation, arterial blood pressure, palpebral and pedal withdrawal reflexes and degree of muscle relaxation were assessed and recorded every 5 minutes. Quality of induction and recovery were assessed. Duration of induction, immobilization and recovery were recorded. Blood samples were analysed for aspartate aminotransferase, creatine kinase and lactate dehydrogenase concentrations. The protocols were compared using paired t tests, Wilcoxon's signed-rank test with Bonferroni's corrections and linear mixed effect models where appropriate.

Results

Out of nine animals, apnoea was noted in eight animals administered protocol BUP-A and two animals administered protocol BUT-A. With TRA-A and control protocols, apnoea was not observed. No other significant differences in any of the parameters were found; however, low arterial blood pressures and hypoxia occurred in TRA-A.

Conclusions and clinical relevance

Our study employing different premedications suggests that the previously published dose of 16 mg kg?1 alfaxalone is too high when used with premedication because we found a high incidence of complications including apnoea (BUP-A), hypotension and hypoxaemia (TRA-A). Appropriate monitoring and countermeasures are recommended.  相似文献   

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