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1.
OBJECTIVE: To evaluate disposition of fentanyl in goats after IV and transdermal administration. ANIMALS: 8 healthy 2-year-old goats weighing 31.8 to 53.6 kg (mean+/-SD, 40.4+/-7.5 kg). PROCEDURE: Each goat was given 2 treatments consisting of fentanyl administered IV (2.5 microg/kg of body weight) and via a transdermal patch (50 microg/h). There was a 2-month interval between treatments. Blood samples were collected at specified times and analyzed in duplicate to determine plasma fentanyl concentrations. Pharmacokinetic values were calculated, using a computerized modeling program. RESULTS: Administration of fentanyl was tolerated by all goats. Intravenous administration of fentanyl resulted in a transitory increase in rectal temperature that was not clinically important. Terminal elimination half-life after IV administration was 1.20+/-0.78 h, volume of distribution at steady state was 1.51+/-0.39 L/kg, and systemic clearance was 2.09+/-0.62 L/kg/h. Transdermal administration of fentanyl resulted in variable plasma concentrations, with peak plasma concentrations ranging from 1.12 to 16.69 ng/ml (mean+/-SD, 6.99+/-6.03 ng/ml) and time to peak concentration ranging from 8 to 18 hours (mean+/-SD, 13+/-4.5 hours). After removal of the transdermal patch, mean+/-SD terminal elimination half-life was 5.34+/-5.34 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fentanyl (2.5 microg/kg) in goats results in a relatively short half-life that will limit its use for management of pain. Transdermal administration of fentanyl (50 microg/h) in goats results in variable plasma concentrations that may exceed those anticipated on the basis of a theoretical delivery rate, but stable plasma concentrations of fentanyl may not be achieved.  相似文献   

2.
OBJECTIVE: To compare postoperative discomfort assessed by subjective pain score and plasma cortisol concentrations in cats undergoing onychectomy that received analgesia by use of transdermal fentanyl (TDF) patches or an i.m. injection of butorphanol. DESIGN: Randomized prospective clinical trial. ANIMALS: 22 client-owned cats weighing 2.2 to 5 kg (4.84 to 11 lb) undergoing onychectomy. PROCEDURE: Researchers were blinded to which cats received a TDF patch (25 microg/h) 18 to 24 hours prior to surgery or an i.m. injection of butorphanol (0.2 mg/kg (0.09 mg/lb]) at the time of sedation, immediately following extubation, and at 4-hour intervals thereafter for 12 hours. Clinical variables, plasma cortisol concentration, and pain scores were evaluated and recorded 24 hours prior to surgery, at extubation, and 2, 4, 8, 12, 24, 36, and 48 hours after surgery. RESULTS: The TDF group had a lower pain score than the butorphanol group only at 8 hours after surgery. Both groups had significantly lower mean plasma cortisol concentrations 0, 24, 36, and 48 hours after surgery, compared with mean plasma cortisol concentrations prior to surgery. No significant differences in appetite or response to handling the feet were observed between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Our data did not reveal a difference in pain relief between administration of TDF and butorphanol. Plasma cortisol concentrations were not different between groups. Fentanyl appeared to provide equivalent analgesia to butorphanol in cats undergoing onychectomy. The primary advantage of using a TDF patch is that repeated injections are not required.  相似文献   

3.
REASONS FOR PERFORMING STUDY: Although fentanyl has been reported to cause CNS excitation in horses, a transdermal therapeutic system (TTS) containing this mu agonist has recently been used empirically in equine medicine to treat moderate to severe pain. A better understanding of the disposition of fentanyl following transdermal administration would facilitate the clinical use of TTS fentanyl to obtain analgesia in horses. OBJECTIVES: To determine the pharmacokinetics of fentanyl following i.v. and TTS patch administration in healthy, mature horses and to evaluate the tolerance of horses to TTS fentanyl administration. METHODS: The pharmacokinetics of fentanyl in serum were assessed following a single i.v. dose, a single TTS dose, and multiple TTS doses in 6 healthy horses. Physical examinations, haematology and serum biochemistry analyses during transdermal fentanyl application were then performed to determine tolerance of continuous fentanyl administration. RESULTS: Fentanyl was very rapidly and completely absorbed following a single TTS dose. Mean serum fentanyl concentrations consistent with analgesia in other species were reached by 1 h and maintained until 32 h after patch application. Similar steady state serum concentrations were obtained when multiple doses of TTS fentanyl were administered every 48 or 72 h over 8 or 9 days, with less fluctuation in serum concentrations during the 48 h dosing interval. Three horses exhibited brief (< 12 h) episodes of increased body temperature; however, transdermal fentanyl administrations were not associated with other significant changes in haematology and biochemistry panels or physical examination findings. CONCLUSIONS AND POTENTIAL RELEVANCE: Although the pharmacodynamics of fentanyl have not been investigated fully in horses, transdermally-administered fentanyl exhibited a favourable pharmacokinetic profile without clinically relevant side effects and may be a useful analgesic in equine patients.  相似文献   

4.
Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2mg/kg) and a 95mg immediate-release RDZ capsule (mean 28.2mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.  相似文献   

5.
Objective To measure the plasma fentanyl concentrations achieved over time with transdermal fentanyl patches in awake cats and cats undergoing anesthesia and ovariohysterectomy. Study design Randomized prospective experimental study. Animals Twenty‐four purpose‐bred cats. Methods Cats were randomly assigned to three groups for Part I of a larger concurrent study. Group P received only a 25 μg hour?1 transdermal fentanyl patch. Group P/A received the patch and anesthesia. Group A received only anesthesia. After a minimum 1‐week washout period, the cats were randomly reassigned to two groups for Part II of the larger study. Group P/A/O received the patch, anesthesia and ovariohysterectomy. Group A/O received anesthesia and ovariohysterectomy. Patches were left in place for 72 hours and plasma samples were obtained for fentanyl analysis while the patches were in place, and for 8 hours after patch removal for cats in Group P, P/A, and P/A/O. Results The 25 μg hour?1 transdermal fentanyl patches were well tolerated by the cats in this study (mean body weight of 3.0 kg) and no overt adverse effects were noted. Mean plasma fentanyl concentrations over time, mean plasma fentanyl concentrations at specific times (8, 25, 49, and 73 hours after patch placement), time to first detectable plasma fentanyl concentration, time to reach maximum plasma fentanyl concentration, maximum plasma fentanyl concentration, mean plasma fentanyl concentration from 8 to 73 hours, elimination half‐life, and total area under concentration (AUC) were not statistically different among the groups. Conclusions Halothane anesthesia and anesthesia/ovariohysterectomy did not significantly alter the plasma fentanyl concentrations achieved or pharmacokinetic parameters measured, when compared with awake cats. There was a high degree of individual variability observed both within and between groups of cats in parameters measured. Clinical significance The high degree of variability observed suggests that careful observation of cats with fentanyl patches in place is required to assess efficacy and any potential adverse effects. Anesthesia and anesthesia/ovariohysterectomy do not appear to alter plasma fentanyl concentrations achieved by placement of a 25 μg hour?1 transdermal fentanyl patch when compared to cats not undergoing these procedures.  相似文献   

6.
Data allowing rational use of analgesics in cats are limited. Pharmacokinetics and pharmacodynamics of fentanyl were studied in cats. Plasma fentanyl concentrations were measured using radioimmunoassay in a crossover study in six cats after 10 microg/kg (i.v.) or by application of fentanyl in pluronic lecithin organogel (PLO) to the inner ear pinna. On a separate occasion thermal thresholds were measured after i.v. fentanyl (10 microg/kg) or saline. Plasma fentanyl concentrations reached 4.7-8.31 ng/mL 2 min after i.v. administration and were undetectable after 95 min. Fentanyl was not detected in plasma at any time after PLO use. Thermal thresholds did not change following saline administration but were increased above baseline from 5 to 110 min after i.v. fentanyl. In this model a plasma concentration of >1.07 ng/mL was required to provide analgesia. Plasma concentrations were measured in additional cats after intranasal or oral dosing (2 microg/kg) and after 30 microg/kg in PLO gel. After oral and nasal dosing, Cmax values were 0.96 and 1.48 ng/mL at 5 and 2 min, respectively. Plasma fentanyl was not detected after application of the higher dose of fentanyl in PLO.  相似文献   

7.
The purpose of the study was to determine pharmacokinetics of fentanyl after intravenous (i.v.) and transdermal (t.d.) administration to six adult alpacas. Fentanyl was administered i.v. (2 μg/kg) or t.d. (nominal dose: 2 μg kg?1 hr?1). Plasma concentrations were determined using liquid chromatography–mass spectrometry. Heart rate and respiratory rate were assessed. Extrapolated, zero‐time plasma fentanyl concentrations were 6.0 ng/ml (1.7–14.6 ng/ml) after i.v. administration, total plasma clearance was 1.10 L hr?1 kg?1 (0.75–1.40 L hr?1 kg?1), volumes of distribution were 0.30 L/kg (0.10–0.99 L/kg), 1.10 L/kg (0.70–2.96 L/kg) and 1.5 L/kg (0.8–3.5 L/kg) for V1, V2, and Vss, respectively. Elimination half‐life was 1.2 hr (0.5–4.3 hr). Mean residence time (range) after i.v. dosing was 1.30 hr (0.65–4.00 hr). After t.d. fentanyl administration, maximum plasma fentanyl concentration was 1.20 ng/ml (0.72–3.00 ng/ml), which occurred at 25 hr (8–48 hr) after patch placement. The area under the plasma fentanyl concentration‐vs‐time curve (extrapolated to infinity) after t.d. fentanyl was 61 ng*hr/ml (49–93 ng*hr/ml). The dose‐normalized bioavailability of fentanyl from t.d. fentanyl in alpacas was 35.5% (27–64%). Fentanyl absorption from the t.d. fentanyl patch into the central compartment occurred at a rate of approximately 50 μg/hr (29–81 μg/hr) between 8 and 72 hr after patch placement.  相似文献   

8.
The tolerance of cephalexin in 10 cats was studied after oral administration of coated tablets (Cefaseptin; Chassot and Cie AG). Over a period of 21 days, the drug was administered twice daily at doses of 25, 30, 50 and 75 mg/kg body-weight. While the first three dose rates were well tolerated clinically, the highest dose was not. After seven days of treatment, signs of intolerance were salivation, vomiting and diarrhoea. Biochemical and haematological parameters (determined in blood, plasma and urine) were not altered. Plasma and skin concentrations of cephalexin were measured after oral treatment of cats with 25 and 50 mg cephalexin/kg body-weight. After treatment with 25 mg/kg body-weight, a mean elimination plasma half-life of 1–7 hours was calculated. The cephalexin concentration measured in the skin after two hours ranged from 8 to 22 per cent of the plasma level, so it is questionable if sufficiently high skin concentrations for efficacy are achieved with doses of 25 mg/kg body weight.  相似文献   

9.
ObjectiveTo characterize the pharmacokinetics of fentanyl and the tolerance of foals to the drug following a single application of a commercially available transdermal system (TS).Study designProspective experimental study.AnimalsSix (two male, four female) foals aged 4–8 days, weighing 56–74 kg.MethodsAfter placement of a jugular sampling catheter, one fentanyl TS (FTS) containing 10.2 mg fentanyl, released at 100 μg hour−1, was applied for 72 hours. Blood samples were withdrawn over the course of 90 hours for fentanyl plasma analysis. Before and after the study, weight, complete blood count and blood chemistry values were obtained. During the study, tolerance and safety were monitored by physical examination and assessment of behavior.ResultsFentanyl was detected as early as 20 minutes after FTS placement. Peak plasma concentrations were variable (0.1–28.7 ng mL−1), were reached after 14.3 ± 7.6 hours (mean ± SD), and returned to baseline concentrations 12 hours after FTS removal. All foals satisfactorily tolerated the FTS application and no significant adverse effects were observed. Rectal temperature increased above 38.5 °C (max. 39.0 °C) in all foals, although this did not correlate with fentanyl plasma concentrations. Results of hematological and biochemical analyses were within reference ranges.Conclusion and clinical relevance Our data show that 100 μg hour−1 fentanyl administered by an FTS results in time-related but variable plasma concentrations in foals. The FTS was easy to apply and was well tolerated.  相似文献   

10.
Fluconazole (100 mg) was administered to six adult cats as an intravenous infusion over 30 minutes, and the same cats received 100 mg of the drug orally 16 weeks later. The cats were bled repeatedly through an indwelling jugular catheter, the plasma fluconazole concentrations were assayed by high performance liquid chromatography, and the concentration-time data were subjected to a non-compartmental pharmacokinetic analysis. The mean (SD) intravenous half-life (13·8 [2·6] hours) was similar to that observed after oral dosing (12·4 [3·0] hours). The plasma clearances (intravenous 0·9 [0·1], oral 0·9 [0·2] ml min−1 kg−1) and the volumes of distribution at steady state (intravenous 1·1 [0·1], oral 1·0 [0·1] litre kg−1) were also similar after the two routes of dosing. The peak plasma concentration was reached 2·6 hours after oral dosing and the drug was completely bioavailable (1·09 [0·05]). On the basis of this single dose study, the administration of 50 mg fluconazole every eight hours to a 4 kg cat should produce average steady state plasma fluconazole concentrations of approximately 33 mg litre−1.  相似文献   

11.
12.
The pharmacokinetics of promethazine were determined in seven camels (Camelus dromedarius) after an intravenous dose of 0.5 mg kg body weight.-1 The data obtained (median and range) were as follows: the elimination half-life (t1/2 beta) was 5.62 (2.84-6.51) h; the steady state volume of distribution (Vdss) was 8.90 (7.10-12.00) L kg-1, total body clearance (CT) was 24.5 (17.22-33.65) ml kg-1 min-1 and renal clearance (Clr) was 4.81 (1.97-5.48) ml kg-1 min-1.  相似文献   

13.
OBJECTIVE: To determine bioavailability, pharmacokinetics, and safety for transdermal (TD) and oral administration of fluoxetine hydrochloride to healthy cats. ANIMALS: 12 healthy mixed-breed sexually intact 1- to 4-year-old purpose-bred cats. PROCEDURE: A single-dose pharmacokinetic study involving 3 groups of 4 cats each was conducted in parallel. Fluoxetine in a formulation of pluronic lecithin organogel (PLO gel) was applied to the hairless portion of the pinnae of cats at 2 dosages (5 or 10 mg/kg), or it was administered orally in capsules at a dosage of 1 mg/kg. Plasma samples were obtained and submitted for liquid chromatography-mass spectrometry-mass spectrometry analysis of fluoxetine and its active metabolite, norfluoxetine. RESULTS: Peak fluoxetine concentration (Cmax) was lower and time to Cmax longer for TD administration versus oral administration. Relative bioavailability of each dose administered via the TD route was 10% of the value for oral administration of the drug. Mean plasma elimination half-life after oral administration was 47 and 55 hours for fluoxetine and norfluoxetine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence that fluoxetine in a 15% (wt:vol) PLO gel formulation can be absorbed through the skin of cats into the systemic circulation. However, the relative bioavailability for TD administration is approximately only 10% of that for the oral route of administration.  相似文献   

14.
The aim of this study was to evaluate the disposition of cyclosporine after intravenous (i.v.) and oral administration and to evaluate single sampling times for therapeutic monitoring of cyclosporine drug concentrations in cats. Six adult male cats (clinically intact) were used. Two treatments consisting of a single i.v. cyclosporine (1 mg/kg) and multiple oral cyclosporine (3 mg/kg b.i.d p.o. for 2 weeks) doses. Whole blood cyclosporine concentrations were measured at fixed times by high performance liquid chromatography and pharmacokinetic values were calculated. Mean values for the i.v. data included AUC (7413 ng/mL.h), t1/2 distribution and elimination (0.705 and 9.7 h, respectively), Cmax (1513 ng/mL), and Vd(ss) (1.71 L/kg). Mean values for the oral data included AUC (6243 ng/mL.h), t1/2 of absorption and elimination (0.227 and 8.19 h, respectively), and Cmax (480.0 ng/mL). Bioavailability of orally administered cyclosporine was 29 and 25% on days 7 and 14 respectively. Whole blood comment cyclosporine concentration 2 h after administration (C2) better correlated with AUC on days 7 and 14 than trough plasma concentration (C12). The rate of oral cyclosporine absorption was less than expected and there was substantial individual variation. Therapeutic drug monitoring strategies for cyclosporine in cats should be re-evaluated.  相似文献   

15.
BackgroundIsavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats.ObjectivesTo determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose.AnimalsEight healthy, adult research cats.MethodsFour cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra‐high performance liquid chromatography‐tandem mass spectrometry. Data were analyzed using a 2‐compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y2 weighting for IV administration. Predicted 24 and 48‐hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed.ResultsBoth PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half‐life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%.Conclusions and Clinical ImportanceIsavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long‐term isavuconazole use are needed.  相似文献   

16.
17.
The pharmacokinetics and metabolism of meloxicam was studied in camels (Camelus dromedarus) (n = 6) following intravenous (i.v.) administration of a dose of 0.6 mg·kg/body weight. The results obtained (mean ± SD) were as follows: the terminal elimination half-life (t(1/2β) ) was 40.2 ± 16.8 h and total body clearance (Cl(T) ) was 1.94 ± 0.66 mL·kg/h. The volume of distribution at steady state (V(SS)) was 92.8 ± 13.7 mL/kg. One metabolite of meloxicam was tentatively identified as methylhydroxy meloxicam. Meloxicam and metabolite were excreted unconjugated in urine. Meloxicam could be detected in plasma 10 days following i.v. administration in camels using a sensitive liquid chromatography tandem mass spectrometry (LC/MS/MS) method.  相似文献   

18.
Six horses were administered either 15 or 20 mg/kg body weight (b.w.) procainamide (PA) as an intravenous (i.v.) dose over 10 min. The plasma concentrations of PA and N-acetylprocainamide (NAPA) as well as the pharmacodynamic effect (prolongation of the QT interval) were monitored. The PA plasma concentrations could be described by a one-compartment model with a t ½ of 3.49 ± 0.61 h. The total body clearance of PA was 0.395 ± 0.090 1/hr/kg and the volume of distribution was 1.93 ± 0.27 l/kg. As observed after PA administration, NAPA (an active metabolite) had a t ½ longer than PA of 6.31 ± 1.49 h. Peak NAPA concentrations (1.91 ± 0.51 μg/ml) occurred at 5.2 h after the PA i.v. dose. The ratio of area under the curves for NAPA to PA was 0.46 ± 0.15 which is similar to that expected in humans classified as slow acetylators. Percentage change in the QT interval was examined with respect to PA and PA + NAPA plasma concentrations. For PA, %ΔQT = 41.2 log (PA) - 13.26 and correlations ( r ) ranged from 0.77 to 0.91 among the horses. In the case of PA + NAPA,%ΔQT= 57.3 log(PA+NAPA)-31.83 andrangedfrom0.77to0.90. No evidence of toxicity was noted with respect to changes in the PR interval.  相似文献   

19.
The pharmacokinetics of primaquine was studied in calves of 180–300 kg live weight. Primaquine was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously (IV) or subcutaneously (SC) and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high-performance liquid chromatography. The extrapolated concentration of primaquine at zero time after IV administration was 0.50±0.48 µg/ml (mean ±SD) which decreased with an elimination half-life of 0.16±0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.50±0.08 µg/ml at 1.67±0.15 h after IV administration. The corresponding value was 0.47±0.07 µg/ml at 5.05±1.20 h after SC administration. The elimination half-lives of carboxyprimaquine after IV and SC administration were 15.06±0.99 and 12.26±3.06 h, respectively. The areas under the concentration-time curve for carboxyprimaquine were similar following either IV or SC administration of primaquine; the values were 11.85±2.62 µg.h/ml after the former and 10.95±2.65 µg.h/ml after the latter. The mean area under the concentration-time curve for primaquine was less than 0.1 µg.h/ml after either route of administration.Abbreviations AUC area under the concentration-time curve - CPRQ carboxyprimaquine - IV intravenous - 6M8AQ 6-methoxy-8-aminoquinoline - PRQ primaquine - SC subcutaneous  相似文献   

20.
Quinocetone (QCT), an antimicrobial growth promoter, is widely used in food‐producing animals. However, information about pharmacokinetics (PK) of QCT in ducks still remains unavailable up to now. In this study, QCT and its major metabolites (1‐desoxyquinocetone, di‐desoxyquinocetone and 3‐methyl‐quinoxaline‐2‐carboxylic) in ducks were studied using a simple and sensitive UHPLC‐MS/MS assay. Twenty ducks were divided into two groups. (n = 10/group). One group received QCT by oral administration at dose of 40 mg/kg while another group received QCT intravenously at 10 mg/kg. Plasma samples were collected at various time points from 0 to 96 hr. QCT and its major metabolites in duck plasma samples were extracted by 1 ml acetonitrile and detected by UHPLC‐MS/MS, with the gradient mobile phase that consisted of 0.1% formic acid in water (A) and acetonitrile (B). A noncompartment analysis was used to calculate the PK parameters. The results showed that following oral dosing, the peak plasma concentration (Cmax) of QCT was 32.14 ng/ml and the area under the curve (AUCINF_obs) was 233.63 (h ng)/ ml. Following intravenous dosing, the Cmax, AUCINF_obs and Vss_obs were 96.70 ng/ml, 152.34 (h ng)/ ml and 807.00 L/kg, respectively. These data indicated that the QCT was less absorbed in vivo following oral administration, with low bioavailability (38.43%). QCT and its major metabolites such as 1‐desoxyquinocetone and 3‐methyl‐quinoxaline‐2‐carboxylic were detected at individual time points in individual ducks, while the di‐desoxyquinocetone was not detected in all time points in all ducks. This study enriches basic scientific data about pharmacokinetics of QCT in ducks after oral and intravenous administration and will be beneficial for clinical application in ducks.  相似文献   

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