ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00206.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Brown, S.A., Jacobson, J.D., Hartsfield, S.M. Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs. J. vet. Pharmacol. Therap.16, 419–425.Midazolam, a water‐soluble benzodiazepine tranquilizer, has been considered by some veterinary anaesthesiologists to be suitable as a combination anaesthetic agent when administered concurrently with ketamine because of its water solubility and miscibility with ketamine. However, the pharmacokinetics of midazolam have not been extensively described in the dog. Twelve clinically healthy mixed breed dogs (22.2–33.4 kg) were divided into two groups at random and were administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) either as an intravenous bolus over 30 s (group 1) or as an i.v. infusion in 0.9% NaCl (2 ml/kg) over 15 min. Blood samples were obtained immediately before the drugs were injected and periodically for 6 h afterwards. Serum concentrations were determined using gas chromatography with electron‐capture detection. Serum concentrations were best described using a two‐compartment open model and indicated at½αof 1.8 min andt½β.p of 27.8 min after i.v. bolus, andt½αf 1–35 min andt½βof 31.6 min after i.v. infusion. The calculated pharmacokinetic coefficient B was significantly smaller after i.v. infusion (429 ± 244 ng/ml) than after i.v. bolus (888 ± 130 ng/ml,P =0.004). Furthermore,AUCwas significantly smaller after i.v. infusion (29 800 ±6120 ng/h/ml) than after i.v. bolus (42 500 ± 8460 ng/h/ml,P<0.05), resulting in a largerClBafter i.v. infusion (17.4 ± 4.00 ml/min/kg than after i.v. bolus (12.1 ± 2.24 ml/min/kg,P<0.05). No other pharmacokinetic value was significantly affected by rate of i

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00207.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Qiao, G.‐L., Fung, K.‐F. Pharmacokinetic‐pharmacodynamic modelling of meperidine in goats (I): pharmacokinetics. J. vet. Pharmacol. Therap.16, 426–437.Plasma and cerebrospinal fluid (CSF) pharmacokinetics of meperidine were investigated after intramuscular (i.m.) or intravenous (i.v.) administration at a dose of 5 mg/kg in adult goats. After i.m. dosing, the plasma profile was best described by a one‐compartment open model. In healthy (n = 16) and postoperative (n = 16) goats, the parameters were, respectively: /max8.3 ± 3.9 and 9.2 ± 5.5 min, Vd2.763 ±1.231 and 3.929 ±2.101 1/kg,Clb0.125 ± 0.036 and 0.087 ± 0.025 1/kg/min,Kc0.0563 ± 0.0358 and 0.0271 ± 0.0136 min‐1. The plasma profile was best fitted by a two‐compartment open model following i.v. injection. In this case, the parameters for healthy(n= 7) and post‐operative(n= 13) goats were, respectively:Vd5.212 ± 1.992 and 5.085 ± 2.288 1/kg,Clb0.096 ± 0.028 and 0.075 ± 0.026 1/kg/min, P 0.0211 ± 0.0093 and 0.0160 ± 0.0052 min.‐1. There were, however, a few individuals with a prolonged elimination phase. Bioavailability of i.m. meperidine was 66.5 ± 15.8% in healthy(n= 6) goats, but much higher in postoperative (n = 10) ones at 94.6 ± 30.0%. Meperidine diffused into and out of CSF according to a first‐order rate process. The time‐course of CSF drug concentration was simulated by a biexponential function. CSF kinetic parameters of i.m. meperidine for healthy(n =7) and postoperative (n = 13) goats were: elimination rate constant(Kei)0.0269 ± 0.0131 and 0.0305 ± 0.0177 min“1, peak CSF concentration time(Tnaxl)15.9 ± 5.0 and 17.0 ± 6.9 min. For the i.v. dosed healthy(n =6) and postoperative(n =8) animals,Kelwas 0.0408 ± 0.0107, 0.0414 ± 0.0123 min‐1and 7maxtwas 10.0 ± 5.0 and 7.7 ± 2.5 min, respectively. It was demonstrated that an obviously lower peak concentration can be reached significantly later in CSF than in plasma, and the kinetic behaviour of meperidine in plasma is different from that in the CSF, indicating meperidine analgesia might not be predic

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00208.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Rose, M.L., Semrad, S.D., Putnam, M.L., Brown, S.A. Effect of endotoxin on tirilazad mesylate (U74006F) pharmacokinetic parameters in neonatal calves.J. vet. Pharmacol. Therap. 16, 438–445.The pharmacokinetics of the 21‐aminosteroid tirilazad mesylate (U74006F) were studied in both healthy and endotoxin‐challenged neonatal calves. Group I calves received a 3‐h intravenous (i.v.) infusion of sterile saline (250 ml) and tirilazad mesylate (1.5 mg/kg i.v.) 1 h after the start of the saline infusion. Group II calves received tirilazad mesylate 1 h after the start of a 3‐h endotoxin (3.25m̈g/kg) infusion. The data obtained indicate that tirilazad mesylate follows a biexponential equation in neonatal calves. The area‐derived volume of distribution (Vdarea) was 9.68 ± 0.759 1/kg in healthy calves and 6.53 ± 1.20 1/kg in endotoxin‐challenged calves (P<0.05). Similarly, significant(P<0.05) decreases in steady‐state volume of distribution (Vjss) and central volume (VJ were observed in endotoxin‐challenged calves (5.32 ± 0.979 1/kg and 1.68 ± 0.189 1/kg, respectively) compared to healthy calves (7.58 ± 0.834 1/kg and 2.43 ± 0.452 1/kg, respectively). A and B were significantly larger in endotoxin‐challenged calves than in healthy calves (P<0.05). Rate constants and their associated half‐lives, area under the curve and clearance were not significantly altered by endotoxin challenge. Serum thromboxane generation(ex vivo)was evaluated as a marker of the drug's physiologic activity. There was no significant difference in thromboxane generation during clotting of blood from healthy and endotoxemic calves tre

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00209.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Weekley, L.B., Eyre, P. Disturbances in ex vivo vascular smooth muscle responses following exposure to Pasturella haemolytica vaccines. J. vet. Pharmacol. Therap.16, 446–453.Rats were vaccinated with saline (control) or one of the two commercially availablePasteurella haemolyticavaccines Presponse or Precon‐PH. Animals were killed 3 days later and thoracic aorta removed for evaluation of theex vivobiophysical responses to carbachol (CCh). In some experiments, vascular endothelium was mechanically removed. Vaccination of rats impairs the endothelial‐dependent relaxation to CCh. In vessels with endothelium removed, the contractile response to CCh is converted into a relaxation following vaccination. Treatment of endothelial‐denuded vascular ringsex vivowith methylene blue, a guanylate cyclase inhibitor, reduced the vaccination effect. Treatment of vascular rings with the superoxide dismutase inhibitor diethyl‐dithiocarbamate, impairs the relaxant reponse of de‐endothelialized vessels to CCh in Presponse vaccinated rats while enhancing the relaxation response of vessels from Precon‐PH vaccinated rats. De‐endothelialized vessels from vaccinated rats, but not control rats, relaxed in the presence of 7V‐monomethyl‐L‐arginine (L‐NMMA), a competitive inhibitor of nitric oxide synthetase. Furthermore, in the presence of L‐NMMA, the relaxant response to CCh is significantly enhanced by Precon‐PH but not Presponse. The normal relaxant response to hydrogen peroxide is converted into a contraction following vaccination. Results suggest that exposure to commercially availableP. haemolyticavaccines alters vascular smooth muscle reactivity to CCh and that several independ

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00210.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

van't Klooster, G.A.E., Blaauboer, B.J., Noordhoek, J.&van Miert, A.S.J.P.A.M. Sulfadimidine metabolism in vitro: II. comparative studies in cultured rat, goat, sheep and cattle hepatocytes. J. vet. Pharmacol. Therap. 16, 454–461.Hydroxylation and acetylation of sulphadimidine (SDD) and the deacetylation of N4‐acetyl SDD was investigated in cultured hepatocytes from male and female rats, from male and female goats and from female sheep and cattle. Significant sex differences were observed for hydroxylation of SDD in hepatocytes from rat and goat. In goat, sheep and cow hepatocytes, the hydroxylation pathway is relatively important, whereas in rat hepatocytes, acetylation is predominant. Hepatocytes of all four species deacetylated N4‐acetyl SDD. In ruminant hepatocytes, deacetylating activity was of considerable importance, whereas in rat hepatocytes, it appeared a minor pathway of metabolism. Similar to thein vivosituation, formation of N4‐acetyl SDD in cultured hepatocytes results from an equilibrium of acetylation and deacetylation. A good correlation was found between results in isolated hepatocytes and previous findingsin vivo, both in levels of species‐related activities and in acetylation‐hydroxylation ratios. In conclusion, cultured hepatocytes appear a usefulin vitromodel to study comparative sulfonamide

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00211.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Rung, K., Riond, J.‐L.&Wanner, M. Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs. J. vetFour dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross‐over study. Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method. Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature. Mean enrofloxacint½λZwas 2.4 h, meanClswas 27.1 ml/min‐kg, and mean Vsswas 7.0 1/kg. After i.v. and p.o. administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (Cmax= 0.2 ng/ml, max = 2.2 h after intravenous administration; Cmax= 0.2 (ig/ml,tmax= 3.6 h after oral administration). A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrof

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00212.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Fairbairn, S.M., Lees, P., Page, C.P., Cunningham, F.M. Duration of antigen‐induced hyperresponsiveness in horses with allergic respiratory disease and possible links with early airway obstruction. J. vet. Pharmacol. Therap. 16, 469–476.Antigen‐induced airway hyperresponsiveness in allergic horses has previously been demonstrated when clinical signs of acute airway obstruction were apparent, as a consequence of exposure of animals to hay and straw for variable periods of time, and repeat measurements of hyperresponsiveness have been made no earlier than 1 week after challenge. In the present study airway responsiveness to methacholine has been measured in normal horses and allergic horses in clinical remission before and 24, 48 and 72 h after a hay and straw challenge of fixed, short, duration (7 h). Correlations between early increases in interpleural pressure and hyperresponsiveness have also been investigated. As in other studies, the mean airway responsiveness of groups of normal and allergic horses in clinical remission was not significantly different. The responsiveness to methacholine of allergic, but not normal, horses was increased after antigen challenge and was significantly greater than that of normal horses at 48 and 72 h after challenge (logPD8 cm: ‐0.77 ± 0.28 vs. 0.27 ± 0.14 at 48 h and ‐0.6 ± 0.25 vs. 044 ± 01 at 72 h;P<0.05). There was also a significant correlation between interpleural presssure at the end of the 7‐h challenge in allergic horses and the increase in responsiveness to methacholine at 24, 48 and 72 h. These results demonstrate that antigen induces an increase in airway responsiveness in allergic horses that persists for up to 3 days and which may be linked to the initial increase in interp

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00213.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Foster, A.P., Cunningham, F.M., Andrews, M.J., Lees, P. A comparison of platelet activating factor (PAF) antagonists WEB 2170 and WEB 2086 in the horse. J. vet. Pharmacol. Therap. 16, 477–487.The effects of the selective platelet activating factor (PAF) receptor antagonist WEB 2170 on PAF‐induced responses in equine cells and tissues have been examined and compared with those of WEB 2086. In initial experiments WEB 2170 was shown to inhibitin vitroplatelet aggregation in a dose‐dependent, competitive reversible manner (pA2= 7.21). Co‐administration of the antagonists with either PAF or histamine also inhibited PAF, but not histamine, induced wheal formation and PAF‐induced neutrophil accumulationin vivoin equine skin. Intravenous (i.v.) administration of both drugs at a dose of 0.1 mg/kg blocked PAF‐inducedex vivoplatelet aggregation. The inhibition produced by WEB 2170 was greater and, at 30 min, this drug also reduced the slope and maximal response. Wheal formation in the skin was significantly inhibited for up to 6 h by WEB 2170 administered i.v., the reduction being more prolonged than that obtained with WEB 2086. Neutrophil accumulation in the skin was also significantly reduced for up to 24 h by WEB 2170, whilst no significant inhibition was produced by WEB 2086. These results demonstrate that WEB 2170, like WEB 2086, is an effective antagonist of PAF in the horse. Moreover, when given i.v., WEB 2170 appears to be a more potent PAF inhibitor th

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00214.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Reid, J., Nolan, A.M., Welsh, E. Propofol as an induction agent in the goat: a pharmacokinetic study. J. vet. Pharmacol. Therap. 16, 488–493.The pharmacokinetics of propofol, 4 mg/kg, administered as a bolus dose intravenously (i.v.) prior to the maintenance of anaesthesia with halothane in oxygen, were determined in five goats, and a clinical impression of its use as an induction agent was made. Induction of anaesthesia was rapid and smooth, providing satisfactory conditions for intubation in all animals. Post‐induction apnoea occurred in one goat and minimal regurgitation of ruminal contents was recorded in two animals. Recovery times were rapid with a mean time to standing after halothane inhalation ceased of 13.7 min. The blood propofol concentration time profile was best described by a bi‐exponential decline in all five goats. The mean elimination half‐life was short (15.5 min), the volume of distribution at steady state large (2,56 1/kg) and the clearance rapid (275 ml/min.kg). Propofol was shown to be a very satisfactory induction agent in t

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00215.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY