摘要:

The pharmacokinetic behaviour of sulphamethoxazole and trimethoprim was studied after combined intravenous (i.v.) administration at doses of 20 mg/kg and 4 mg/kg, respectively, and after oral administration at doses of 50 mg/kg and 10 mg/kg. The serum concentration versus time data after i.v. administration were best described by the biexponential equations C = 34.77.e‐2.655.t+ 39.03.e‐0.241.tfor sulphamethoxazole and C = 3.29.e‐3.878.t+ 0.83.e‐0.306.tfor trimethoprim. Mean biological half‐lives of the drugs were 2.89 ± 0.11 and 2.38 ± 0.33 h, respectively. The distribution volumes (Varea) were 0.475 ± 0.026 l/kg (sulphamethoxazole) and 3.89 ± 0.61 I/kg (trimethoprirn). Orally administered sulphamethoxazole and trimethoprim were rapidly absorbed. The maximum serum concentrations were reached 0.5‐1 h after administration. The bioavailability was 8 1% for sulphamethoxazole and 41% f

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00254.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abass, B.T., Weaver, B.M.Q., Staddon, G.E., Waterman, A.W. Pharmacokinetics of thiopentone in the horse.J. vet. Pharmacol. Therap.17, 331–338.The pharmacokinetics of thiopentone sodium administered intravenously as a single dose (11 mg/kg) were studied in acepromazine pre‐medicated horses and ponies in which anaesthesia was maintained with either halothane (Group 1) or isoflurane (Group 2). The results showed that the disposition kinetics of thiopentone in horses and ponies were best described by a three‐compartment open model. In plasma, a very short initial distribution phase in both horses and ponies, half‐life 1.4 ± 1.2 min (mean ± SD) and 1.3 ± 0.7 min, respectively, was obtained, which was followed by a second comparatively slower redistribution phase, half‐life 16 ± 12 min and 11 ± 5 min, respectively. The volume of distribution for the drug was large, especially in the ponies which received isoflurane (1127 ± 86 ml/kg). compared to the horses which received halothane (742 ± 89 ml/kg). The drug had a somewhat shorter elimination half‐life in the horses (147 ± 21 min) than in the ponies (222 ± 44 min), but no obvious difference in clearance of the drug was observed between the horses (3.5 ± 0.5 ml/min/kg) and ponies

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00255.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetics and metabolic fate of labelled compounds were investigated after intramuscular administration of3H‐radiolabelled etiproston to nine cows. Elimination was rapid (t1/2β= 2.8 h). Forty‐eight h after administration 92.6% of the radioactivity had been eliminated, mainly via the urinary (66% at 48 h) and faecal routes (26% at 48 h). In comparison, little elimination in milk occurred (less than 0.034% dose/l by 24 h). Radioactivity at the injection site 48 h after administration was seen in one cow (<4.68 × 10‐5% dose/g). No radioactivity was detected in the tissues. Urinary metabolites were purified and isolated using XAD‐2 extraction and preparative HPLC in reverse and normal phases. The main urinary metabolite, identified by mass spectrometry, was the tetranor acid derivative in equilibrium with its lac

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00256.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The effects of peripheral (intravenous, i.v.) and central (intracerebroventricular, ICV) administrations of agonists of 5‐HT1A, 5‐HT2, 5‐HT3and 5‐HT4receptors were investigated in conscious sheep chronically fitted with intraparietal electrodes on the reticulum and the dorsal, ventral and caudo‐ventral rumen. The 5‐HT1Aagonist 8‐hydroxydipropylaminotetralin increased reticular and decreased ruminal spike burst frequency when given i.v. (80 μg/kg) and ICV (8 μg/kg). The 5‐HT2and 5‐HT3agonists, α‐methylserotonin and 2‐methylserotonin, induced a moderate inhibition of rumino‐reticular contractions when given i.v. at 100 and 150 μg/kg, respectively, while marked inhibition was observed after ICV administration at doses of 10 and 5 μg/kg, respectively. The 5‐HT4agonist 5‐methoxytryptamine strongly stimulated rumino‐reticular motility by the ICV (10 μg/kg) route, whereas it induced a moderate inhibition when administered i.v. (200 μg/kg). The selective antagonist of 5‐HT1A, 5‐HT2, 5‐HT3and 5‐HT4receptors, spiroxatrine, ritanserin, granisetron and DAU 6285, respectively, blocked the responses of the respective agonists given by the same route. Moreover, the antagonists given ICV blocked the effects of the agonists given i.v. except for DAU 6285 ICV, which did not antagonize the inhibition induced by 5‐methoxytryptamine i.v. It is concluded that the four types of serotonergic receptors investigated control rumino‐reticular motility at the central level. However, according to the receptor type and the forestomach area (reticulum or rumen) this control may be stimulatory or inhibitory, demonstrating a pleiotropic role of serotonin in t

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00257.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Concentrations of the non‐steroidal anti‐inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi‐compartmental model with two successive rate constants ka1= 0.05 ± 0.06 h‐1and ka2= 0.06 ± 0.01 h‐l. Alclofenac half‐livest½andt1/2βwere 1.0 ± 0.8 h and 6.9 ± 1.5 h, respectively. Maximal concentrations (38.9 ± 16.2 μg/ml) were obtained after 8.5 ± 2.4 h. Alclofenac was detected in urine for at least 48 h after dosing. The percentage of the dose excreted as unchanged alclofenac in 12 h was very low (0.68 ± 0.19%), total (free + conjugated) alclofenac accounted for 2.1

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00258.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetics of ampicillin and sulbactam administered in combination were studied in calves and sheep. The animals were administered an aqueous solution of ampicillin/sulbactam (2: 1, w/w) intravenously and intramuscularly at doses of 13.2 and 6.6 mg.kg‐1, respectively. A microbiological method was used to detect ampicillin, and HPLC was used to detect sulbactam in serum. Following intravenous (i, v.) administration, the distribution phases were rapid and similar (about 15 min) for both drugs in both species, whereas sulbactam in calves and ampicillin in sheep showed a faster elimination rate. After intramuscular (i.m.) administration both drugs showed peak concentrations higher in calves than in sheep: the peak time of sulbactam was shorter in calves than in sheep. No other significant differences in the pharmacokinetics of the combination were observed between the species after i.m. injection. The mean residence and absorption times, calculated by non‐compartmental analysis, for both calves and sheep suggested that the differences in ampicillin and sulbactam phgrmacokinetics could be attributable to the different molecular structu

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00259.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetics of thiamphenicol were investigated in 10 calves and six lactating cows. It was found that this drug is rapidly absorbed (1 5 min) following intramuscular injection with an absorption rate constant and a bioavailability of 8.7 h‐1and 84%, respectively. The drug appears to be widely distributed into various body fluids, yielding a volume of distribution (Vd(area)) of approximately 0.9 l/kg. The micro‐rate constants indicated that the antibiotic rapidly diffuses into the peripheral compartment (k12>k21). Elimination from plasma is relatively rapid, with a biological half‐life of about 1.75 h. Thiamphenicol appears shortly in milk (15 min) after its intravenous administration, and gives milk to plasma concentration ratios greater than one between 4 and

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00260.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A pharmacokinetic study of gentamicin (5 mg/kg intravenous (i.v.)) was conducted first in cinically healthy female goats and then in the same goats after induction of fever byEscherichia coliendotoxin (0.2 μg/kg i.v.). Rectal temperature increased 1 to 1.5°C in febrile goats. Differences in the blood serum concentrations of gentamicin were not observed at any time between febrile and normal goats. The disposition kinetics of gentamicin were described by a biex‐ponential expression CP= Ae‐αt+ Be‐β. Median values for the half‐lives of gentamicin were 103.6 min in normal and 136.0 min in febrile goats. The apparent volume of distribution (Vd) was 263.3 ml/kg in the febrile goats which was not different from that in the normal goats (240.6 ml/kg). The volume of the central compartment (Vc) was almost identical in normal and febrile goats. The body clearance (Clβ) was observed to be 1.7 and 1.6 ml/min‐kg in normal and febrile goats, respectively. Dosage regimens for gentamicin were calculated on the basis of media

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00261.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The responses of equine blood platelets in citrated platelet‐rich plasma to arachidonic acid, U44069 (prostaglandin endoperoxide analogue), adenosine 5′‐diphosphate, platelet‐activating factor or collagen were investigated by turbidimetric aggregometry. Pre‐treatment of the platelets with aspirin (1 mmol/1) or Paracetamo1 d‐3 mmol/1) abolished shape change and aggregation in response to arachidonic acid; decreased the rate of aggregation in response to collagen, with no separate effect on shape change; had no marked effect on aggregation caused by the other agonists; but in no case transformed irreversible aggregation to reversible aggregation. We conclude that thromboxane A2generation is of minor importance in the aggregation of equine platelets, and in particular that thromboxane A2is not a significant mediator of irreversible

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00262.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The contractile effects of the tachykinins eledoisin, substance P and neurokinin A and B were investigatedin vitroon circular and longitudinal muscle strips from horse duodenum, ileum and colon. Circular smooth muscle of the small intestine was highly responsive, large intestine circular smooth muscle less so, while longitudinal muscle from all gut segments was much less sensitive. pD2values and intrinsic activities on small intestine circular muscle indicated differences in receptor distribution between the duodenum and ileum: NK3and a smaller number of NK2receptors being present in the duodenum, and NK2receptors predominating in the ileum. Notwithstanding this, eledoisin and neurokinin B were the most active substances on duodenum and ileum, respectively. These findings suggest that tachykinins may play a role in equine gastrointestinal pathophysiology.

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00263.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY