摘要:

The fate of skeletal muscle‐derived creatine kinase (CK) was investigated in six dogs. After i.m. and i.v. injections of 3000gand 105 000gsupernatants of dog muscle homogenates, plasma CK activity was measured up to 48 h. There was no significant difference in pharmacokinetic parameters dependent on the type of supernatant injected. After i.v. injection, the volume of distribution of CK was equal to the plasma volume, CK clearance was relatively low (about 0.5 mL/kg/min) and its terminal half‐life of elimination was about 2.5 h. After i.m. injection, the CK terminal half‐life was about 6.5 h, demonstrating a flip‐flop mechanism, i.e. a limiting absorption process from the site of injection. Bioavail‐ability after i.m. injection was about 65%, and the rate of absorption from muscle injection site was relatively slow: peak activity occurred at the second hour post administration, and most CK activity had been absorbed by 24 h. These pharmacokinetic parameters can be used as a basis for a minimally invasive means of quantitating muscle damage either after intramuscular drug administration or in canine sports

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00542.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The pharmacokinetics of ciprofloxacin was investigated in healthy, mature ponies. Ciprofloxacin was administered intravenously to six ponies at a dose of 5 mg per kg body weight. Seven days later, ciprofloxacin was administered orally to each pony at the same dose. Intravenous ciprofloxacin concentration vs. time data best fit a two‐compartment open model with first‐order elimination from the central compartment. Mean plasma half‐life, based on the terminal phase, was 15 7.8 9 min (harmonic mean). Total body clearance of ciprofloxacin was 18.12 ± 3.99 mL/min/kg. Volume of distribution at steady‐state was 3.45 ± 0.72 L/kg. From the pharmacokinetic data and reported minimum inhibitory concentrations for equine gram‐negative pathogens, the appropriate dosage of ciprofloxacin was determined to be 5.32 mg per kg body weight at 12 h intervals. Bioavailability of oral ciprofloxacin in ponies was 6.8 ± 5.33%. Owing to the poor bioavailability, a dosage regimen could not be proposed for oral ciprofloxacin administration in horses. Ciprofloxacin concentrations were determined in tissues and body fluids at 1, 2 and 4 h after intravenous administration. At all times, tissue concentrations exceeded plasma concentrations of ciprofloxacin. Highest concentrations were achieved in kidneys and urine. Potentially therapeutic concentrations were obtained in cerebrospinal and joint fluid, but low concentrations were achieved in aq

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00543.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The haemodynamic effects of hyoscine‐N‐butylbromide (0.30 mg/kg, intravenously) were studied in eight adult ponies in a blinded two‐period crossover experiment with repeated measures. Values for heart rate were 63%, 48% and 13% greater than control values at 1, 16 and 46 min, respectively, after administration of hyoscine‐N‐butylbromide. Cardiac output increased by 16% at 16 min after drug injection. Mean right atrial pressure was decreased by 79%, 63%, 45% and 52% at 1, 16, 46 and 61 min, respectively, after drug administration. Stroke volume was decreased by 32% at 1 min and pulmonary arterial wedge pressure was decreased by 44% at 16 min. We detected no significant difference in mean systemic arterial pressure, mean pulmonary arterial pressure, systemic vascular resistance or pulmonary vascular resistance at

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00544.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The object of this study was to examine whether prolonged‐release hard gelatin capsule formulations could be developed for dogs. Different viscosity grades of hydroxypropyl methylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were used to control drug release. Furosemide was chosen because of its wide use in the management of heart failure in dogs. Invitro, selecting different viscosity grades allowed good control of drug release, whereas in vivo the difference between formulations was clearly smaller. Although all formulations gave prolonged release, both inter‐ and intra‐individual variation in the plasma concentration‐time curves was high. It is difficult to develop prolonged‐release formulations for drugs such as furosemide with highly variable pharmacokinetic properties. However, hard gelatin capsules containing hydrophilic polymers could still be a suitable choice for s

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00545.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

A radioreceptor assay technique is described for the measurement of xylazine and medetomidine in sheep plasma. The assay was based on the displacement of tritiated clonidine from a 2‐adrenoceptors in a rat brain homogenate by xylazine or medetomidine extracted from plasma. Plasma samples from sheep which had been given xylazine and medetomidine were treated with alumina to remove endogenous catecholamines which would otherwise have bound to α2‐‐adrenoceptors and interfered with the assay. The drugs were then extracted using chloroform, reconstituted in buffer and used to displace [3H]clonidine. The concentration of α2‐agonist was calculated by reference to standard curves. The method had a detection limit of 2.5 ng/mL for xylazine and 0.24 ng/mL for medetomidine. The assay could also be used to detect metabolites capable of binding to α2

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00546.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The purpose of this study was to evaluate the pharmacokinetics of cyclosporine (Cy) in woodchucks (Marmota monax) and Pekin ducks. These data are needed to design rational dosing regimens. Pharmacokinetic parameters were calculated from blood concentration‐time data obtained following intravenous (i.v.) administration of 10 mg/kg body weight to woodchucks and Pekin ducks. Whole blood samples were collected in EDTA and assayed using a commercially available radioimmunoassay kit that employs a monoclonal antibody specific for Cy. The blood concentration‐time profile best Dtted an open, two‐compartmental model in Pekin ducks. Compartmental analysis of data in woodchucks did not adequately describe the data. When non‐compartmental pharmacokinetic analysis of the data was performed, the resulting mean (± SD) pharmacokinetic parameters in woodchucks and Pekin ducks, respectively, were as follows: volume of distribution at steady‐state, 2.9 (± 0.8) and 2.7 (± 0.2) L/kg; systemic clearance, 10.2 (± 2.8) and 28.6 (± 6.1) mL/kg/min; mean residence time, 4.8 (± 1.1) and 1.6 (± 0.3). These data suggest that Pekin ducks clear Cy at a faster rate than do woodchucks and that a greater dose of Cy should be administered to Pekin ducks in order to achieve adequate i

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00547.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

A rabbit model for simultaneous investigation of the bioavailability, tissue residues and tissue tolerance of intramuscularly administered veterinary medicines is described. The bioavailability of ampicillin from two intramuscular products, which had been found to be different in calves, were compared in a two‐way crossover design. The ampicillin levels in plasma, ampicillin residues in tissues, the plasma creatine kinase activity and the tissue damage at the injection sites were studied. The absolute bioavailabilities for the products were 100% and 40%. Differences in pharmacokinetics of ampicillin between sexes were observed after intravenous and intramuscular administration. Only slight tissue damage could be detected at the injection sites after intramuscular administration of these products. The results were compared with those obtained previously in calves and were found to be similar. Further investigations with other intramuscular drug products to validate this model are under wa

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00548.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Azithromycin is the first of a class of antibiotics classified as azalides. In an initial experiment four cats were given a single dose of azithromycin 5 mg/kg orally (p.o.), followed 2 weeks later by a single intravenous bolus (i.v.) dose of 5 mg/kg. Subsequently, six cats were given [14C]azithromycin p.o. in a single dose of 5.4 mg/kg for the study of tissue distribution and metabolism. In both experiments, serial blood samples were collected and the plasma assayed for unchanged azithromycin to determine various pharmacokinetic parameters. After p.o. administration, bioavailability was 58% and absorption rapid with atmaxof 0.85±0.72 h and a Cmaxof 0.97 ± 0.65 μg/mL The harmonic mean terminal t1/2after i.v. administration was 35 h. Tissue half‐lives varied from 13 h in fat to 72 h in cardiac muscle. Three metabolites were identified in bile. Unchanged azithromycin accounted for 100% of the total radioactivity in lung and skin tissues when assayed. In comparison with other species, the bioavailability in cats is higher than in humans but lower than in dogs. As in the dog,>50% of the azithromycin‐related material in feline bile was unchanged azithr

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00549.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In the present study, the pharmacokinetic parameters of a trimethoprim/sulphachlorpyridazine preparation following intravenous administration, administration by nasogastric tube and administration with concentrate were determined in the horse. Eight adult horses were dosed at 1 week intervals in a sequentially designed study at a dose of 5 mg/kg trimethoprim (IMP) and 25 mg/kg sulphachlorpyridazine (SCP) on all occasions. Plasma concentrations of both drugs were measured serially for 48 h. Pharmacokinetic parameters of clinical importance (distribution and elimination half‐lives, clearance, bioavail‐ability, volume of distribution) were determined both for TMP and SCP. Following intravenous administration, the volume of distribution at steady‐state (Vd(33)was significantly larger for TMP (1.51 ± 0.25 L/kg than for SCP (0.26 ± 0.05 L/kg. The clearance was 7.73 ± 2.26 mL/min‐kg for TMP and 2.64 ± 0.48 mL/min·kg for SCP. For both TMP and SCP, mean peak plasma concentrations (Cmax) and the bioavailabilities (F) were reduced significantly when the drugs were mixed with concentrate (ct) as compared with those after nasogastric administration (ngt) (Fct= 44.3 ± 10.7% vs.Fngt= 68.3 ± 12.5% for TMP;Fct= 46.3 ± 8.9% vs.Fngt= 67.3 ±13.7% for SCP). Following the administration of TMP and SCP mixed with concentrate, the plasma concentration—time curves showed a biphasic absorption pattern in all horses. The first peak occurred 1–2 h and the second peak 8–10 h after administration of the combination preparation. Based on the pharmacokinetic data obtained and the publishedin vitrosensitivity data, it may be predicted that TMP and SCP given intravenously or by nasogastric tube at a dose of 5 mg/kg and 25 mg/kg respectively and a dosage interval of 8–12 h would result in sufficiently high plasma concentrations for effectiveness against susceptible bacteria. The single oral administration of TMP and SCP mixed with concentrate did not result in effective plasma concentrations. Further studies are needed to investigate whether higher plasma concentrations would be achieved by a multiple dosing

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00550.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The purpose of this study was to examine the effects of midazolam on the nociceptive threshold responses in sheep. The intravenous administration of midazolam (0. 1–0.3 mg/kg) produced a significant dose‐dependent elevation of the mechanical and thermal nociceptive thresholds. The intravenous administration of flumazenil (20 μg/kg) markedly attenuated the antinociceptive activity of midazolam in the mechanical nociceptive test, whereas intravenous naloxone (0.2 mg/kg) had no significant effect on midazolam‐mediated analgesia. The intrathecal administration of midazolam (1 mg), via chronically implanted cervical subarachnoid catheters, produced a significant elevation in the mechanical threshold responses. These results indicate that midazolam has antinociceptive actions in the sheep and suggest that this effect is, at least partially, mediated at the spinal

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00551.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY