ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00713.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The pharmacokinetics of thiopentone was studied in six mongrel dogs using a high‐performance liquid chromatographic method for measurement of the drug in the plasma. An intravenous bolus dose (20 mg/kg) of 2.5% thiopentone sodium solution was injected into the cephalic vein. While the two‐ and three‐compartment models were used in the analysis of the experimental data, the disposition curve was adequately described by a biexponential equation. Plasma protein binding of thiopentone was determinedin vitrousing the equilibrium dialysis technique. The drug was bound to a moderately high extent (73.8 ± 4.1%). The half‐time of the initial phase, which comprises distribution/redistribution, was 14.9 ± 3.3 mins. The apparent volume of distribution was quite high for an organic acid (843 ± 194 ml/kg). This may be attributed to the high lipid solubility of the thiobarbiturate. The half‐life was 6.99 ± 2.18 h and a body clearance value of 1.51 ± 0.60 ml/kg‐min was obtained. It can be concluded from this study that the half‐time of the distribution/redistribution phase approximates the duration of anaesthetic effect. Consequently, physiological conditions and disease states which influence distribution/redistribution rather than those affecting hepatic biotransformation of the drug are likely to

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00714.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The pharmacokinetic disposition of xylazine hydrochloride is described after both intravenous and intramuscular injection of a single dose, in four domestic species: horse, cattle, sheep and dog, by an original high performance liquid chromatographic technique. Remarkably small interspecific differences are reported. After intravenous administration, systemic half‐life (t1/2 β) ranged between 22 min (sheep) and 50 min (horse) while the distribution phase is transient with half‐life (t1/2 α) ranging from 1.2 min (cattle) to 5.9 min (horse). The peak level of drug concentration in the plasma is reached after 12–14 min in all the species studied following intramuscular administration. Xylazine bioavailability, as measured by the ratios of the areas under the intravenous and intramuscular plasma concentrationversustime curves, ranged from 52% to 90% in dog, 17% to 73% in sheep and 40% to 48% in horse. The low dosage in cattle did not permit calculation. Kinetic data are correlated with clinical data and the origins of interspecific differences are di

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00715.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Xylazine is an effective sedative analgesic that induces vomiting in the cat. A consistently effective intramuscular emetic dose of xylazine was established in normal cats in this laboratory. Animals in which the area postrema of the medulla oblongata had been chronically destroyed did not exhibit emesis in response to the standard test dose of xylazine but continued to show sedation. By contrast, sham‐operated cats responded normally. Refractoriness to deslanoside, a known specific emetic drug, was used as functional proof for successful ablation of area postrema, and the lesions were also validated histologically. We conclude that xylazine exerts its emetic action on the chemoreceptor trigger zone of the area postrema. It is suggested that this action may be mediated by an opiate type of molecular receptor

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00716.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Pupillary response to xylazine (10–300 μg/kg, i.v.) norepinephrine (1–30 μg/kg, i.v.) and atropine (3–100 μg/kg, i‐v.) were observed in rats anaesthetized with pentobarbital. Xylazine caused a dose‐dependent mydriasis which was antagonized by a selective α2‐adrenergic blocking agent, yohimbine (2.5 mg/kg, i.v.). A non‐selective adrenergic blocking agent, phentolamine (2.5 mg/kg, i.v.) was less effective in antagonizing this effect of xylazine. A selective α1‐adrenergic blocking agent, prazosin (2.5 mg/kg, i.v.) was ineffective in reducing the xylazine‐induced mydriasis. In contrast, both phentolamine and prazosin blocked the pupillary dilation produced by norepinephrine, while yohimbine was much less effective in antagonizing norepinephrine‐induced mydriasis. Atropine also induced a dose‐dependent mydriasis which was not affected by yohimbine pre‐treatment. The present study suggests that the mydriatic effect of xylazine in the rat is mediated by an adrenergic mechanism, possibly by stimulating the α2‐adrenergi

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00717.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The pharmacokinetics of theophylline were investigated in dogs following intravenous, single oral, and multiple oral doses of aminophylline. Mean half‐life (t1/2) of theophylline following single intravenous administration was 5.7 h and the apparent specific volume of distribution (V'darea) was 0.82 litre/kg. The bioavailability of theophylline was high (91%) following oral administration of aminophylline tablets and the absorption half‐life (t1/2 ab) was 0.4 h.Theophylline plasma concentrations observed following repeated oral administration of aminophylline tablets were somewhat greater than predicted. This suggests that theophylline plasma concentrations should be monitored and the dosage regimen individually adjusted in critically ill anim

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00718.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Dogs were treated with the anti‐epileptic drug valproic acid (VPA) for 2 weeks in order to determine whedier therapeutic plasma levels could be maintained. VPA (as the sodium salt) was administered in a dosage of 170–180 mg/kg/day divided into three equal doses in the form of enteric‐coated tablets. Due to the rapid elimination of this drug in dogs, therapeutic plasma levels were reached only intermittently. However, the concentrations maintained may be sufficient for anti‐epileptic therapy in dogs because the lower plasma protein binding of VPA in this species gives rise to higher central concentrations compared with man. Furthermore, some VPA metabolites previously shown to exert anticonvulsant activity (2‐en‐VPA and 3‐keto‐VPA) were found in relatively high concentrations in dog plasma.We would recommend the dosages used in this study as a basis for assessment of VPA in the treatment of

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00719.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

A method for the analytical determination of metronidazole concentrations in biological tissues was developed using high performance liquid chromatography. The procedure was employed to investigate the pharmacokinetics of metronidazole in dogs following intravenous and oral administration (44 mg/kg). The overall elimination rate constant β was 0.0027 ± 0.0005 min‐1, the apparent specific volume of distribution (V'd) was 0.948 ± 0.096 L/kg overall clearance (ClB) was 2.49 ± 0.54 ml/kg/min and the rate constant for absorption Kabwas 0.0456 ± 0.0353 min‐1. Oral bioavailability was high but variable (59%–100%). Implications of these data for chemotherapy of infections caused by anaerobic bacteria, trichomonads, and Giardia and for the sensitization of hypoxic neoplastic cells to radiotherapy are

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00720.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Lidocaine was administered intravenously on several occasions to three healthy mongrel dogs. The lidocaine treatment consisted of an infusion of 0.8 mg/kg/ min over 10 min, followed by an infusion of 0.085 mg/kg/min over 3 h. This lidocaine treatment was given once in the awake state and on two other occasions the infusion was started before or during the following anaesthetic regimen: atropine‐meperidine premedication, thiopental induction and maintenance nitrous oxide‐methoxyflurane anaesthesia.In most instances plasma levels were somewhat higher at the end of the loading infusion (>5 μg/ml) than subsequendy, but steady‐state values were obtained soon after starting the 3‐h infusion. There were no striking differences between the plasma profiles and half‐lives found in the three series of experiments: mean plasma concentrations of lidocaine during steady state were between 3.5 and 5.0 μg/ml and the half‐life of lidocaine was 1 to 2 h.Signs of intoxication were not seen in any of the dogs at any stage of the procedures. It is concluded that with the loading and maintenance doses used in this study steady‐state values, probably within the therapeutic range, are obtained within a few minutes. The plasma concentrations are not influenced by the anaesthet

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00721.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Warfarin was administered intravenously (i.v.) as a single dose of 1.5 mg/kg to healthy dogs and the pharmacokinetic parameters were investigated. Elimination could be described by a one‐compartment open model. Values for the elimination half‐life and apparent specific volume of distribution were 14.5 ± 4.1 h and 0.22 ± 0.04 litre/kg, respectively. Oral maintenance doses were calculated from the data collected following i.v. administration and administered every 12 h for a total of five doses after an initial i.v. loading dose of 1.5 mg/kg. Prothrombin times increased from a control value of 8.6 ± 0.3 sec to 55.2 ± 5.2 sec over a period of 96 h. Prothrombin time returned to control values by 62 h after withdrawal of the drug. We propose a dosage regimen of warfarin for anticoagulant therapy in the dog of 0.22 mg/kg to be given orally every 12 h. Prothrombin time should be monitored during therapy and the dose of warfarin modified according to the degree of suppression of coagulation factors

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1981.tb00722.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY