摘要:

Six Welsh gelding ponies (weight 246 ± 6 kg) were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) followed by 0.02 mg/kg of detomidine i.v. Anaesthesia was induced with 2 mg/kg of ketamine i.v. Ponies were intubated and lay in left lateral recumbency. On one occasion anaesthesia was maintained for 2 h using 1.2% halothane in oxygen. The same group of ponies were anaesthetized 1 month later using the same induction regime and anaesthesia was maintained with a combination of detomidine, ketamine and guaiphenesin, while the ponies breathed oxygen‐enriched air. Electrocardiogram, heart rate, mean arterial blood pressure, cardiac output, respiratory rate, blood gases, temperature, haematocrit, glucose, lactate and cortisol were measured and cardiac index and systemic vascular resistance were calculated in both groups. Beta‐endorphin, met‐enkephalin, dynorphin, arginine vasopressin (AVP), adrenocorticotrophic hormone (ACTH) and catecholamines were measured in the halothane anaesthesia group only and 11‐deoxycortisol during total intravenous anaesthesia (TIVA) only. Cardiorespiratory depression was more marked during halothane anaesthesia. Hyperglycaemia developed in both groups. Lactate and AVP increased during halothane anaesthesia. Cortisol increased during halothane and decreased during TIVA. There were no changes in the other hormones during anaesthesia. Recovery was smooth in both groups. TIVA produced better cardiorespiratory performance and suppressed the endocrine stress response observed during halothane ana

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00046.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We determined the haemodynamic, electrocardiographic and electrophysiologic effects, and the pharmacokinetic properties of 4′‐hydroxypropranolol (4′‐OHP) by conducting three different experiments in dogs. In experiment 1 the plasma concentrations of 4′‐OHP (mg/kg, i.v.) in pentobarbital anaesthetized dogs were determined by HPLC and pharmacokinetic parameter values were estimated. The terminal elimination half‐life (t1/2) for 4′‐OHP was 69.4 min, the apparent volume of distribution (Vd) was 3.39 L/kg and the total clearance (Clt) was 53.6 mL/min·kg. These data were subsequently used to calculate the loading and maintenance doses of 4′‐OHP required to produce targeted steady‐state plasma concentrations for 4′‐OHP of 30, 60, 120, 240 and 480 ng/mL. In experiment 2 the haemodynamic and electrocardiographic effects for target plasma concentrations of 4′‐OHP were determined in two groups of pentobarbital anaesthetized dogs, and beta‐blocking activity was assessed by infusion or bolus doses of isoproterenol. The haemodynamic and electrocardiographic effects of the target plasma concentrations (30, 60, 120 ng/mL) of 4′‐OHP were first determined in seven pentobarbital anaesthetized dogs (Group 1). Beta blocking activity was assessed by the infusion of 0.1 μg/kg/min isoproterenol. The infusion of 4′‐OHP produced dose dependent decreases in heart rate, cardiac output, dP/dtmax, mean arterial pressure and left ventricular diastolic pressure. The PR interval of the lead II electrocardiogram increased and the QTcinterval decreased. These haemodynamic and electrocardiographic changes became apparent at plasma 4′‐OHP concentrations equal to or greater than 30 ng/mL. Plasma concentrations of 4′‐OHP equal to or greater than 30 ng/mL prevented the haemodynamic and electrocardiographic effects of isoproterenol infusion. In group 2 dogs, (seven dogs) the haemodynamic and electrocardiographic effects of target plasma concentrations (30, 60, 120, 240, 480 ng/mL) of 4′‐OHP were evaluated and beta‐blocking activity was assessed by the i.v. bolus administration of 1 and 4 μg/kg of isoproterenol. The infusion of 4′‐OHP produced haemodynamic and electrocardiographic changes similar to those in group 1 dogs. In addition, the QRS duration of the electrocardiogram increased at plasma concentrations of 4′‐OHP equal to or greater than 240 ng/mL. The haemodynamic and electrocardiographic effects of i.v. bolus dose administrations of 1 and 4 μg/kg isoproterenol were abolished by plasma concentrations of 4′‐OHP equal to or greater than 240 ng/mL. In experiment 3 we determined the electrophysiologic effects of 10−9to 10−5mmol/L 4′‐OHP on Tyrodes superfused bundles of canine Purkinje fibres. Action potential duration and the effective refractory period decreased at superfusate concentrations of 4′‐OHP equal to or greater than 10−7mmol/L. Action potential overshoot, action potential total amplitude, the rate of rise of phase O (dV/dt) and spontaneous rate decreased at superfusage concentrations of 4′‐OHP equal to or greater than 800 ng/mL. These studies demonstrate that: 1) 4′‐OHP produces haemodynamic, electrocardiographic and electrophysiologic effects similar to those of other beta‐blocking drugs in pentobarbital

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00047.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Sixteen healthy male dogs were used at random in this protocol. The dogs were anaesthetized with isoflurane in oxygen. Eight of the dogs received 0.25 mg/kg of butorphanol (group B) and the others an equal volume of isotonic saline (group S) administered by a catheter inserted in the lumbosacral epidural space. Butorphanol concentrations in plasma and cerebrospinal fluid (CSF) were measured using high‐performance liquid chromatography with electrochemical detection. Maximum concentration of butorphanol and time to obtain this concentration were 42.28 ng/mL at 13.88 min in blood, and 18.03 ng/mL at 30 min in CSF. Volume of distribution, clearance, mean distribution and elimination half‐lives were respectively 4.39 L/kg, 2.02 L/h.kg, 16.5 min and 189.1 min. Mean isoflurane minimal alveolar concentration values for group B obtained following hind‐ or forelimb stimulation decreased by 31% after epidural butorphanol. Cutaneous analgesia (to pin‐prick test) persisted for 3 h after the end of isoflurane anaesthesia in group B and was in correlation with the plasmatic analgesic dose of butorphanol (9 ng/mL). These results suggested that analgesia was predominantly obtained by action of butorphanol on the supraspinal structures following its vascular systemic abs

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00048.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The pharmacokinetic parameters of doxycycline (DOX) were determined in 3 day, 3‐, 6‐ and 12‐week‐old fasted turkeys, after a single intravenous (i.v.) dose of 25 mg doxycycline. HCl/kg body weight. Doxycycline disposition fitted an open two‐compartment model. The mean (± SD) elimination half‐life was 10.6 ± 0.7, 10.8 ± 1.5, 7.9 ± 1.4 and 10.0 ± 0.9 h in 3 day, 3‐, 6‐ and 12‐week‐old turkeys, respectively. Mean (± SD) total body clearance was 0.19 (± 0.01), 0.27 (± 0.03), 0.11 (± 0.03) and 0.06 (± 0.01) L/h.kg in 3 day, 3‐, 6‐ and 12‐week‐old turkeys, respectively. The steady‐state volume of distribution was 1.77 (± 0.2), 2.1 (± 0.2), 0.7 (± 0.4) and 0.5 (± 0.2) L/kg in turkeys of the above mentioned ages, respectively. TheAUCvalue significantly increased with the age of the turkeys. An oral doxycycline solution at a single dose of 25 mg/kg of body weight was administered to 3 day, 3‐, 6‐ and 12‐week‐old turkeys. The maximal plasma concentrations in fasted turkeys were 3.8, 5.6, 7.4 and 5.7 μg/mL, withtmaxvalues of 4.7, 1.5, 2.8 and 5.4 h, for the different ages, respectively. In fed turkeys theCmaxvalues were 2.5, 6.1, 4.8 and 3.0 μg/mL, withtmaxvalues of 4.2, 5.3, 4.5 and 7.5 h, respectively. The absolute bioavailability in fasted turkeys varied between 25.0 ± 9.0% (for 12‐week‐old birds) and 63.5 ± 7.1% (for 3‐week‐old birds). The relative bioavailability varied between 40.0 ± 13.0%

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00049.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Binding of antibiotics to food has received little attention in equine medicine, although such binding could potentially reduce the bioavailability and clinical efficacy. In the present study, binding of trimethoprim (TMP) and sulphachlorpyridazine (SCP) to hay, grass silage and concentrate was investigatedin vitroin buffer at pH 6.8 at different concentrations. The binding of TMP and SCP to caecal contents was also studied. In addition, the degradation of TMP and SCP by the caecal microflora was investigated by incubating sterilized and non‐sterilized caecal contents for 3 h at 37° under anaerobic conditions and comparing the TMP and SCP contents. Further, a TMP/SCP powder formulation was adminstered orally with concentrate at a dose rate of 5 mg/kg TMP and 25 mg/kg SCP to three ponies with a caecum fistula; the animals were deprived of food for 8 h before administration. Blood samples, caecal contents samples and faecal samples were collected and analysed for TMP and SCP concentrations by means of high performance liquid chromatography (HPLC). Three non‐fistulated ponies, acting as control animals, were fed the same dose of TMP/SCP with concentrate after 8 h of food deprivation and blood samples were taken. The percentage ofin vitrobinding of TMP as well as SCP to hay, grass silage and concentrate at concentrations of 4 μg/mL to 10 μg/mL was high (60‐90%). TMP and SCP were also extensively bound to caecal contents (50‐70%). At spiking concentrations above 10 μg/mL the percentage of binding decreased. There was no evidence of biodegradation of TMP or SCP in caecal contents.In vivo, both drugs could be detected in the caecal contents and in the faeces of three fistulated ponies. However, the fistulated ponies differed from the control ponies in that their TMP and SCP plasma concentrations were higher, and two fistulated ponies did not show double peaks in their plasma concentration‐time curves. Therefore, the fistulated ponies did not provide an optimal model forin vivobinding studies. Despite this limitation, it can be concluded that binding of TMP and SCP to food is a major cause of the limited bioavailability of these drugs in the horse. It is hypothesized that the binding is reversible, and that a second absorption phase occurs in the large intestine, but part of the administered dose remains bound as both drugs were found

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00050.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

In the present study the bioavailability of febantel paste and febantel suspension was investigated in the fully hydrated and the dehydrated camel. The serum concentrations of febantel and its metabolites, fenbendazole, oxfendazole and fenbendazole sulfone were determined by high performance liquid chromatography following extraction with ether. The exposure to febantel and its metabolites in fully hydrated camels was significantly higher in camels dosed with febantel paste compared to febantel suspension, as measured byAUCandCmax· TheAUCandCmaxof fenbendazole and oxfendazole were significantly lower in dehydrated camels as compared to control camels dosed with febantel paste. The systemic availability of febantel suspension in control and dehydrated camels was very low and differences between dehydration and control phases were insignificant. The low systemic availability of febantel in camels dosed with febantel suspension may cause nematodes to become resistant to this anthelmintic. It is, thus, suggested to increase the dose of febantel paste in dehydrated camels in order to increase the exposure to febantel and its metabolites. The binding of febantel, fenbendazole, oxfendazole and fenbendazole sulfone to camels’serum proteins was over 85%. Oxfendazole was only about 70% bound. Dehydration of 10 days did not affect the binding of these benzimidazole derivatives to serum protei

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00051.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

To determine whether ivermectin is metabolized in the rumen,in vitrostudies were conducted with the tritium‐labelled H2B1acomponent of ivermectin in rumen fluid from sheep and cattle. No detectable metabolism occurred over 24 h inin vitroincubations at 38°. The viability of the microbes in the rumen fluids was demonstrated by the conversion of 17% and 11% of [14C]cellulose to14CO2in 24 h in the incubations with sheep and steer rumen fluids respectively. The results indicate that ivermectin is not metabolized in the rumen. Based on the lack ofin vitrometabolism of ivermectin in rumen fluid, the similarity ofin vitroliver microsomal metabolism within vivometabolism of the avermectins and the physicochemical properties of the avermectins, any disappearance of ivermectinin vitrofrom rumen fluid is probably a result of binding to solids or surfaces. Apparent discrimination by dung beetles, where observed, between control faeces and faeces from cattle or sheep treated with ivermectin or abamectin therefore must be attributable to chance, to factors unrelated to treatment or to factors such as changes in amino acid composition rather than the production of volatile metabolites of ivermect

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00052.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The kinetics of free and microgranulated sulfadimidine were compared in milk‐fed calves dosed orally (180 mg/kg) in a crossover study. Microgranulation results in delayed absorption of sulfadimidine and poor bioavailability, with the area under the plasma concentration‐time curve (AUC(O‐oo)) reduced from 7400 to 3781 μg·h/mL, and maximum plasma concentration (Cmax) reduced from 188.1 ± 39.0 to 84.41 ± 22.6 μg/mL. It is concluded that sulfadimidine microgranulated with long chain fatty acids is not suitable for use in milk‐fed calves; the gastrointestinal transit time is too rapid to allow full release of the drug, markedly limiting its bioavailability. In adult animals, or in the young of other animal species in which digesta transit time is slower than in calves, the bioavailability of microgranulated sulfadimidine may be

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00053.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) was measured after intravenous and oral administration to pigs. Eighteen healthy pigs (six for each compound) weighing 22‐43 kg received a dose of 10 mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a fasted and a fed condition in a three‐way crossover design. The three tetracyclines were present in plasma up to 30 hours after intravenous and after oral administration to fasted as well as fed pigs. The volume of distribution was 1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The bioavailability was in general low for all the three tetracyclines. The presence of food did not affect the bioavailability of OTC, which was only 3% in both fasted and fed pigs. For TC there was a significantly higher bioavailability in fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not significant, being 11% in fastedvs.6% in fed pigs. Even though the presence of food affected the bioavailability only for TC, it prolonged the absorption phase for all three tetracyclines. Based on the bioavailability and the resulting plasma concentrations, it is concluded that it is not possible to obtain a therapeutically active concentration in plasma or tissues after oral administration of any of the three tetracyclines to fed or fasted p

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00054.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00055.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY