Plasma concentrations of transdermal fentanyl and buprenorphine in pigs (Sus scrofa domesticus)

Objective

To determine the absorption characteristics of fentanyl and buprenorphine administered transdermally in swine.

Effects of propofol and fentanyl on duodenal motility activity in pigs

To investigate the effects of propofol and fentanyl on the postprandial duodenal motility the intraluminal impedance technique was used. Six pigs were instrumented with a central venous catheter, a percutaneous enterogastrostomy (PEG), and an impedance catheter, which was introduced via the PEG into the duodenum through endoscopy. Over the following 3 d, duodenal motility was measured for 8-hour periods. Measurements were taken on each subject under 3 different sets of conditions: in the conscious unrestrained pig, during propofol sedation, and during sedation with propofol-fentanyl. Both, after morning feeding and during gastric nutrition via the PEG, duodenal feeding patterns and duodenal phase II of the migrating motor cycle were shortened during propofol and propofol-fentanyl sedation. In contrast, the duration of phase I was prolonged by propofol and propofol-fentanyl. In conclusion, either propofol or propofolfentanyl sedation shortens duodenal feeding patterns, as well as phase II of the migrating motor cycle.     

The effect of stress conditions on exocrine pancreatic secretion in growing pigs

Introduction   Competition and aggression in pigs is known to reduce daily weight gain (DWG) (R und GREN and L& ouml ; fqvist 1989; H yun et al. 1998; L und et al. 1998), and to impair feed conversion ratio (W alker 1991; L und et al. 1998). The exact biological mechanisms behind these effects are not fully understood. Aggression and competition activate a cascade of reactions of biological relevance, such as inhibition of the parasympathetic nervous system, stimulation of the sympathetic nervous system, including the adrenal medulla (A xelrod et al. 1970; D alin et al. 1993a, 1993b), and activation of the hypothalamo-hypophyseal-adrenal (HHA) axis resulting in higher adrenocorticotropic hormone (ACTH) and higher cortisol concentrations in the plasma (D alin et al. 1993b; O lsson and S vendsen 1997). These responses as well as muscular activity increase metabolic losses (S chrama et al. 1993).
Hyper-physiological treatment with glucocorticoids stimulates pancreatic amylase activities in piglets (B aintner and N emeth 1982; C happle et al. 1989a, 1989b, 1989c), but no observations in growing pigs have been published. Inhibition of the parasympathetic nervous system (C hey et al. 1979) and stimulation of the sympathetic nervous system (C hey 1991) reduce exocrine pancreatic secretion. So, there might be some conflicting physiological responses of the exocrine pancreas to stress conditions. In order to increase our understanding of the animal's physiological responses to conditions of stress, we tested the hypothesis that conditions associated with stress (mixing with unfamiliar pigs, frustration and ACTH treatment) reduce exocrine pancreatic secretion. In addition, we tested the effect of treatment with Amperozide (a neurolepticum which reduces aggression and the effects of stress in pigs) on exocrine pancreatic secretion.     

中草药饲料添加剂对生长肥育猪免疫功能的影响

选用30kg左右的“杜×长×大”三元杂交猪72头,随机分成3组,分别为对照组及添加0.5%、1%中草药试验组,每组3个重复,进行饲养试验及血样采集和血清免疫指标的测定。由试验可知,与对照组相比,在IgM、IgA、C4水平上,两个中草药组与对照组相比无显著差异(P>0.05);而IgG水平,0.5%中草药组比对照组提高12.49%(P<0.05),1%中草药组比对照组提高24.28%(P<0.01);C3水平,0.5%中草药组比对照组提高10.81%(P<0.05),1%中草药组比对照组提高21.62%(P<0.01)。表明中草药饲料添加剂能改善机体的体液免疫功能,增强机体的免疫力,以1%中草药为最佳添加量。     

和胃平喘颗粒对生长猪生长性能的影响

为探求生长猪日粮中添加和胃平喘颗粒对生长猪生长性能的影响,选取80头50 kg左右"杜长大"健康生长育肥猪作为试验动物,根据公母各半、体重相近的原则将其随机分为试验组和对照组,每个组设2个重复,每个重复20头。试验组在每千克基础日粮中添加20 g和胃平喘颗粒(g/kg),对照组饲喂基础日粮。试验结果显示,在生长猪日粮中添加20 g/kg和胃平喘颗粒对生长育肥猪的生长性能没有产生显著影响(P0.05)。     

生长猪饲粮中添加糖蜜酒精废液浓缩物的试验研究

试验选择21头体重15kg左右的杜长大三元杂交生长猪,随机分为3组,每组7头(3公4母),分别在饲粮中添加使用0%(对照组)、3.0%(试验Ⅰ组)和5.0%(试验Ⅱ组)的糖蜜酒精废液浓缩物(MAWC),进行为期21d的饲养试验,结果表明,各组平均日增重差异不显著(P>0.05);与对照组比较,试验Ⅰ组和Ⅱ组日增重分别提高3.70%和0.97%,饲料增重比(F/G)分别降低5.5%和4.7%。消化试验结果表明,饲粮中添加3.0%、5.0%的MAWC,饲粮粗蛋白、粗脂肪、粗纤维等养分的表观消化率有所改善。广西甘蔗糖业副产物资源丰富,研究开发糖蜜酒精废液浓缩物作饲料,可变废为宝,社会效益、经济效益和环境生态效益显著。     

不同剂量半胱胺对生长猪生产性能的影响

试验选择平均体重为16.31kg的杜长大杂交猪118头,随机分为4组。试验一期,半胱胺在基础日粮中添加量为0、50、100、0mg/kg;试验二期,基础日粮中半胱胺添加量为0、100、150、250mg/kg。试验结果表明,试验一期,CS50组(Ⅰ)、CS100组(Ⅱ)平均日增重分别提高4.45%、2.87%,差异不显著;料重比CS50组(Ⅰ)下降5.26%(P<0.05),CS100组(Ⅱ)下降7.69%(P<0.01);试验二期,CS100组(Ⅰ)、CS150组(Ⅱ)、CS250组(Ⅲ)平均日增重分别提高3.98%、5.98%、5.44%,差异均不显著;料重比分别下降2.90%、8.41%(P<0.05)、4.34%。     

Pharmacokinetics of intravenous and transdermal fentanyl in alpacas

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 V_ss, 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.     

Pharmacokinetics and tolerance of transdermal fentanyl administration in foals

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.     

不同饲喂次数对猪生产性能的影响

本试验研究不同饲喂次数对育肥猪生长性能的影响。试验结果表明,生长肥育母猪(平均初始体重60kg)日饲喂2次较为合理。     

Regional differences in transdermal penetration of fentanyl through equine skin

The rate and regional differences for the penetration of fentanyl through equine skin was investigated in vitro using a commercial transdermal therapeutic system (TTS) or ‘patch’. Skin collected from the thorax, groin and leg (dorsal metacarpal) regions of five horses was placed in diffusion cells and a fentanyl TTS applied to each skin sample. Drug penetration through each skin sample over 48 h measured using high performance liquid chromatography (HPLC). Cumulative penetration (μg/cm²) was plotted against time (h) and used to regress the steady state flux (μg/cm²/h) of fentanyl through each skin site. Results showed similar fluxes for both the thorax (2.32 ± 0.17 μg/cm²/h and groin (2.21 ± 0.11 (μg/cm²/h) regions, but significantly lower flux (P = < 0.05) for the leg region (1.56 ± 0.120 μg/cm²/h. Interestingly, there was a significantly longer lag time for the penetration of fentanyl through the groin region (7.87 ± 0.51 h) compared to the other two sites (5.66 ± 0.97 h and 5.75 ± 0.43 h for the thorax and leg regions respectively). The results suggest that a fentanyl TTS applied to the leg region may have a small but significantly lower amount of fentanyl available systemically, compared to patches applied to the thorax or groin regions, which may affect the level of analgesia subsequently achieved in the horse.     

Pharmacokinetics of fentanyl following intravenous and transdermal administration in horses

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.     

The effect of water sprinkling on the performance of growing and finishing pigs during hot weather

Summary Periodic sprinkling of water on growing and finishing pig for 2 minutes at the approximate rate of 50 ml per pig significantly improved their average daily gain and feed conversion. There was little change in feed intake. Sprinkling every 45 minutes gave better results than sprinkling every 90 minutes. If the sprinklers were operated when the temperature was above 25°C, in the growing stage and above 21° in the finishing stage performance was better than it was if they were operated only above 29 and 25°C.

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Sumario Asperiones periodicas de dos minutos en cantidades aproximadas de 50 ml por animal en el período de levante y ceba, mejoró significativemente el promedio de ganancia diaria y la conversión de alimentos. No hubo cambios apreciables en la ingestión de los mismos. Las aspersiones con intervalos de 45 minutos, dieron mejor resultado que las efectuadas cada 90 minutos. Cuando los rociadores funcionaron en temperatureas por encima de los 25°C en el período de levante y por encima de 21°C en período de ceba, el desarrollo fue mejor que cuando funcionaron solamente en temperaturas por encima de 29° y 25°C.

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Résumé Des porcs périodiquement douchés pendant deux minutes avec 50 1. d'eau ont répondu de fa?on significative tant en ce qui concerne le gain journalier de poids que l'utilisation de la nourriture, alors que peu de changements ont été notés dans la quantité de nourritur absorbée. L'affusion d'eau toutes les 45 minutes donne des résultats supérieurs à celle obtenue lorsque l'intervalle entre deux douches est porté à 90 minutes. Les aspersions pratiquées lorsque la température ambiante se situe au dessus de 25° pendant la croissance des animaux et au dessus de 21° lor de leur finition donent de meilleurs résultats que si elles ont respectivement lieu au-dessus de 25 et 29°C.

     

Studies on nitrogen retention in growing pigs

Nitrogen retention (RN) was measured in 60 barrows of Danish Landrace and a total of 470 balance periods was carried out during the growth period from 20 to 85 kg live weight. In the first serie (Expt A) six different feed compounds of high biological value (HBV) were fed to 48 barrows, while in the second serie (Expt B) 12 barrows were measured on feed compounds of HBV or low biological value (LBV). Three different levels of gross energy were used in Expt B. Individual differences of 10-20% in the pigs capability for nitrogen retention were observed. Nitrogen retention increased from 12 to 21 g N/d on the HBV-compounds and was not influenced by increasing nitrogen or energy intake. Nitrogen retention was curvilinear in relation to metabolic live weight (kg0.75) in both series. A parabolic function on kg0.75 gave the best fit to the data with the following regression equations: Expt A + B: RN, g/d = 1.48 LW, kg0.75 - 0.027 LW, kg1.50 (HBV) Maximum = 20.5 g RN/d at 84 kg LW Expt B: RN, g/d = 1.03 LW, kg0.75 - 0.013 LW, kg1.50 (LBV) Maximum = 20.4 g RN/d at 133 kg LW     

Evaluation of transdermal fentanyl patch attachment in dogs and analysis of residual fentanyl content following removal

Objective To investigate whether the method used to attach matrix‐type fentanyl patches influences the degree of skin attachment and the amount of active drug remaining in patches after use. Study design Prospective, randomised clinical study. Study population Fifteen adult dogs of mixed breeds. Methods Two equally sized matrix‐type fentanyl patches were attached to the dorsal third of the lateral thorax of fifteen dogs for 72 hours. The two patches were attached using different techniques: Method AD used an adhesive dressing in combination with a transparent film. Method TG used tissue adhesive applied to the edges of the patch. After 72 hours the patches were removed and the proportion of the patch attached at this time calculated. The residual content of the patches was analysed using a validated gas chromatography–mass spectrometery (GC–MS) analysis technique. Results After 72 hours of continuous attachment, the mean proportion of drug uptake for method AD was 17.2 (SD ± 11.1)% and for method TG this was 16.9 (SD ± 7.3)%. The median proportion of attachment for method AD was 100% and for method TG was 95.6%. Conclusions The method of attachment did not significantly influence the uptake of fentanyl from matrix‐type patches. The method of attachment resulted in a significant difference in the proportion of the patch attached 72 hours after placement, with method AD resulting in a greater median proportion of attachment than TG. Clinical relevance The method used to attach matrix‐type fentanyl patches to dogs should not interfere with drug uptake. The residual fentanyl content remaining in these patches after 72 hours of continuous application is significant and could lead to intoxication if ingested by humans.     

Pharmacokinetics and the effect of application site on a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles

Application of transdermal drugs to different anatomical sites can result in different absorption characteristics. The pharmacokinetics (PKs) and bioequivalence of a single 2.6 mg/kg (50 μL/kg) dose of a novel, long-acting transdermal fentanyl solution were determined when applied topically to the ventral abdominal or dorsal interscapular skin of 40 healthy laboratory Beagles. The PKs were differentiated by a more rapid initial absorption of fentanyl from the dorsal application site. Mean plasma fentanyl concentrations remained above 0.6 ng/mL from 4 to 96 h in the dorsal application group and from 8 to 144 h in the ventral application group. Bioequivalence analysis demonstrated that the sites were not equivalent; the 90% confidence intervals of the ratio of the geometric means for both the maximum concentration (C(max)) and the area under the curve (AUC) were not contained within the 80-125% interval. The C(max) was 2.34 ± 1.29 (mean ± standard deviation) and 2.02 ± 0.84 ng/mL for the ventral and dorsal application groups, respectively. The terminal elimination half-lives (t(1/2)) for both groups were similar with values of 137 ± 58.9 and 117 ± 59.6 h for the ventral and dorsal application site groups, respectively. A mean absorption rate of ≥ 2 μg · kg/h was maintained from 2 to 144 h following dorsal application and from 2 to 264 h following ventral application. These results suggest that transdermal fentanyl solution could be applied as a single dose to the dorsal scapular area 2-4 h prior to surgery with analgesia lasting a minimum of 4 days.     

Sites of nutrient digestion in growing pigs: effect of dietary fiber

The impact of dietary fiber on fecal digestion is well-known and provides a comprehensive approach toward nutrient digestibility and availability. Little quantitative information is available on digestion of fiber in the different segments of the gastrointestinal tract (GIT). The objectives of this study were to obtain a method allowing the quantification of the digestive process in different segments of the GIT and to study the impact of dietary fiber on nutrient digestibility. Six barrows (average initial BW of 30 kg and fitted with a simple T-cannula at the proximal duodenum and caudal ileum) were used in a replicated 3 x 3 Latin square design. In each period, pigs were offered 1 of 3 diets differing in fiber content (low, medium, and high). Differences in fiber content were created by replacing wheat and barley with wheat bran. Titanium dioxide was included in the diet as an indigestible marker to determine the apparent digestibility coefficients in different segments of the GIT. The apparent digestibility of ash, CP, DM, and OM increased in the different segments of the GIT. Duodenal digestibility coefficients were negative for ash (e.g., -39.9% for the medium- and high-fiber diets), indicating important endogenous mineral secretions by the stomach and digestive glands. The duodenal digestibility of other nutrients and OM were positive but close to zero and numerically lower in the diets with the greater fiber contents. The fiber content in the diet did not affect the apparent ileal digestibility of nutrients. Increasing the fiber content in the diet affected the fecal digestibility of CP, ether extract, and energy (P < 0.01). The method used for studying sites of digestion in the digestive tract provides promising results, but it is limited due to the high variability that is likely caused by sampling limitations and variation between animals.