Etodolac is a nonsteroidal anti-inflammatory drug with selective cyclooxygenase-2 inhibition to treat pain and inflammation associated with osteoarthritis in humans and dogs. The aim of the study was to investigate the pharmacokinetics of etodolac following single oral administration of 200?mg to 10 healthy beagle dogs.
The plasma concentrations of etodolac were detected using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was conducted using the noncompartmental method and modeling approaches.
Etodolac was rapidly absorbed (Tmax?=?0.85?h, Ka?=?1.49?h?1) and slowly eliminated (T1/2?=?39.55?h) following oral administration to the dogs. A two-compartment pharmacokinetic model with first-order absorption and elimination rate constants was successfully explained for the pharmacokinetic aspects of etodolac in dogs. From a Monte Carlo simulation (1000 repetitions), the accumulation index and AUCτ at steady state were predicted as 1.60 [90% confidence intervals (CI), 1.24–2.81] and 408.18?ng·hr/mL [90% CI, 271.26–590.58?ng·hr/mL], respectively.
This study will help to enact a more accurate optimal dosing regimen of etodolac in dogs with osteoarthritis, and may be useful in developing a novel formulation of etodolac for human in the future.
目的探索能准确稳定记录犬Oddi括约肌(sphincter of Oddi,SO)肌电活动的新方法,并对记录到的肌电波形进行初步分析。方法用自行研制的黏膜接触式电极记录30只犬SO肌电活动,同时记录十二指肠和胃的肌电活动,分析SO肌电波形的规律以及和胃十二指肠肌电的关系。结果用我们的方法可以记录到犬SO的快波和慢波,同步记录以及切离实验证实记录到的波形是犬的SO肌电而不是来自十二指肠和胃。结论犬的SO肌电记录是可行的,犬SO快波和慢波的发现将对SO功能研究提供一个新的平台。 相似文献
Immunohistochemical and immunoelectron microscopical studies were carried out on 28 aged dogs' brains. Amyloid deposits were seen in the arteries and capillaries in the leptomeninges and in superficial areas of the cortices in 19 (67.9%) of the 28 dogs (10-22 years of age). Immunohistochemically, these amyloid deposits were reactive for anti-beta/A4 antibody. Additionally, a variable number of parenchymal deposits with diffuse beta/A4-immunoreactivity (diffuse plaques) was also noted throughout the cerebral cortex in 24/28 dogs (85.7%). However, these plaque lesions were undetectable in Congo red staining. Electron microscopically, amyloid fibrils, measuring 10 nm in width, were located mainly in the tunica media of the arteries, and in less involved vessels they tended to be present among collagen fibres in the adventitia and smooth muscle cells in the outer layer of the media. The plaque lesions appeared to contain sparse aggregations of amyloid fibrils. In immunoelectron microscopical examinations, all amyloid fibrils in both blood vessels and plaques were selectively labelled by gold particles. These findings indicate that aged dogs can provide a useful experimental model for research into the beta/A4-type of cerebral amyloidosis commonly seen in Alzheimer's disease. 相似文献
Glucocorticoid effects on kainic acid-induced motor seizures and wet dog shakes in rats were investigated by adrenalectomy and dexamethasone treatment. One-day adrenalectomy attenuated kainic acid-induced wet dog shakes and seizure activity. These effects were restored by dexamethasone. Administration of dexamethasone to non-adrenalectomized rats potentiated kainic acid-induced wet dog shakes and severity of seizure activity. These results suggest that glucocorticoids may play an important role in modulating the severity of kainic acid-induced seizures and wet dog shakes. 相似文献
There is growing interest in the possible use of homologous testis transplantation for the treatment of anorchia and male
infertility. In order to test the surgical and immunological feasibility of this therapy, three series of experimental studies
of homologous testis transplantation were carried out in dogs. In the first pilot study, four beagles from the same litter
were transplanted using microsurgical techniques for end-to-end anastomosis of the testicular vessels and the vas deferens.
These dogs received cyclosporin A (CyA) for 3 months after transplantation. The longest functional graft survival in this
series was 163 days, strongly suggesting that long-term survival of a homologously transplanted testis graft is possible.
A second series of operations was performed on ten mongrel dogs. The same surgical technique was employed and the series was
divided into three groups.
Group 1 received CyA monotherapy, group 2 a combination of CyA and prednisolone, and group 3 received no immunosuppression.
The average graft survival time in this series was 18 days, significantly less than the 71 days in the first series. The dogs
in group 2, however, had graft survival times that were three times longer than those in the other two groups, suggesting
that CyA in combination with prednisolone yields the best graft survival. In the third series, five littermates received a
testis graft after castration. Immunosuppression was achieved by administration of CyA and prednisolone for 3 months. In three
out of five animals, the graft survived until the immunosuppressive therapy was suspended. Histological biopsies of the graft
3 months after transplantation showed the same maturation of sperm cells as in the control testis of the same dog. The results
of the last series suggest that long-term survival of homologously transplanted testis grafts in dogs is, indeed, possible
with the aid of CyA and prednisolone.
Received: 14 August 1996 Received after revision: 21 March 1997 Accepted: 24 April 1997 相似文献
The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption. 相似文献