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排序方式: 共有320条查询结果,搜索用时 265 毫秒
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2.
Possible active transport mechanism in pharmacokinetics of flunixin-meglumin in rabbits 总被引:3,自引:0,他引:3
Miyazaki Y Horii Y Ikenaga N Shimoda M Kokue E 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2001,63(8):885-888
The plasma and urine kinetics of flunixin-meglumin (FNX, 2 mg/kg, i.v.) in rabbits were examined. Unusual pharmacokinetic profiles were obtained, including high binding percentage with plasma protein (> 99%), a short elimination half-life (< 4 hr) and a relatively large Vd-area (0.5 L/kg). These profiles indicate that some active transport mechanisms are involved in FNX disposition. The recovery of FNX from urine was approximately 9 % of the dose within 24 hr following the injection. The estimated renal clearance of the unbound drug nearly corresponded to the renal blood flow rates, indicating that active tubular secretion in the renal re-absorptive tract may be involved in the disposition. The effect of a concomitant administration of pravastatin (PV) on FNX disposition was also examined. PV is a representative substrate of a transporter in human liver cells (OATP-2). After the PV administrations, the Vd-area of FNX and total body clearance markedly decreased, indicating that FNX is actively taken up and metabolized in liver cells by an OATP-2 like transporter. In conclusion, there are at least 2 active transport pathways for FNX pharmacokinetics in rabbits, one is renal tubular secretion and the other is in the sinusoidal section of the liver. 相似文献
3.
4.
OBJECTIVE: To evaluate the inhibitory potency of ketoconazole (KTZ) on the metabolic activities of isozymes of cytochrome P-450 (CYP) in dogs. ANIMALS: 4 healthy 1-year-old male Beagles. PROCEDURE: Hepatic microsomes were harvested from 4 dogs after euthanasia. To investigate the effects of KTZ on CYP metabolic activities, 7-ethoxyresorufin, tolbutamide, bufuralol, and midazolam hydrochloride were used as specific substrates for CYP1A1/2, CYP2C21, CYP2D15, and CYP3A12, respectively. The concentrations of metabolites formed by CYP were measured by high-performance liquid chromatography, except for the resorufin concentrations that were measured by a fluorometric method. The reaction velocity-substrate concentration data were analyzed to obtain kinetic variables, including maximum reaction velocity, Michaelis-Menten constant, and inhibitory constant (Ki). RESULTS: KTZ competitively inhibited 7-ethoxyresorufin O-deethylation and midazolam 4-hydroxylation; it noncompetitively inhibited tolbutamide methylhydroxylation. Bufuralol 1'-hydroxylation was inhibited slightly by KTZ. The mean Ki values of KTZ were 10.6+/-6.0, 170+/-2.5, and 0.180+/-0.131 microM for 7-ethoxyresorufin O-deethylation, tolbutamide methylhydroxylation, and midazolam 4-hydroxylation, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, KTZ at a therapeutic dose may change the pharmacokinetics of CYP3A12 substrates as a result of inhibition of their biotransformation. Furthermore, no influence of KTZ on the pharmacokinetics of CYP1A1/2, CYP2C21, and CYP2D15 substrates are likely. In clinical practice, adverse drug effects may develop when KTZ is administered concomitantly with a drug that is primarily metabolized by CYP3A12. 相似文献
5.
Disease-induced variations of plasma albumin (ALB) and alpha 1-acid glycoprotein (AAG) levels were investigated in dogs. Lower ALB (sometimes > 50% reduction) and higher AAG (sometimes > 10-fold increase) levels were observed in dogs with various diseases. Drug binding was determined at therapeutic concentrations using normal, low-ALB and high-AAG dog plasma. The binding percentages of the ALB-binding drugs decreased in low-ALB plasma, resulting in a large increase in unbound drug, particularly for naproxen (a 13-fold increase). The binding percentages of all AAG-binding drugs investigated in this study increased in high-AAG plasma, resulting in a large decrease in unbound drug, particularly for quinidine (99% decrease). The fluctuation in the unbound fraction of drugs could affect their efficacy or could cause side-effects. Veterinary clinicians should monitor the ALB and AAG levels in the plasma of patients and correct dosage regimens according to these levels, where field conditions permit this, in order to ensure the proper usage of drugs with high affinity for ALB or AAG. 相似文献
6.
Shimoda T Shiranaga N Mashita T Hasegawa A 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2000,62(1):59-64
Hematological abnormalities were investigated in 13 cats with myelodysplastic syndrome (MDS). Examination of the peripheral blood samples from the 13 cats revealed anemia in 11 cats, leukopenia in 9 cats, and thrombocytopenia in 9 cats. Four cats had pancytopenia (30.8%) and 9 cats had bicytopenia (69.2%). Dysplastic changes of erythrocytes, neutrophils, and platelets in the peripheral blood were found in 5, 10 and 8 cats, respectively. Bone marrow examination of the 13 cats revealed that ratios of blast cells to all nucleated cells (ANC) ranged from 0 to 20%. Ratios of erythroid progenitor cells to ANC were more than 50% in 3 cats and less than 50% in 10 cats. Eosinophils accounted for more than 5% of non-erythroid cells in 10 cats. Dysplastic changes in the granurocytic, erythrocytic, and megakaryocytic cells in the bone marrow were found in 11, 7 and 5 cats, respectively. Dysplastic changes in these cats included giant neutrophils, ring-nucleated neutrophils, binuclear myelocytes, hypersegmented and hyposegmented neutrophils, megaloblastoid erythroblasts, multinucleated erythroblasts, micromegakaryocytes, and segmented multinucleated megakaryocytes. Virological examination indicated the presence of feline leukemia virus antigen in the peripheral blood from all of the 13 cats with MDS. The peripheral blood cytopenias and dysplastic changes in each blood cell lineage in the bone marrow were shown to be important for the diagnosis of MDS in cats. 相似文献
7.
Shimoda T Shiranaga N Mashita T Hasegawa A 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2000,62(1):113-115
A one-year old castrated male cat was admitted to the hospital with vomiting and diarrhea. Laboratory examination revealed pancytopenia and positive for FeLV antigen. A bone marrow examination indicated necrosis of the nucleated cells. Based on these findings, the cat was diagnosed as bone marrow necrosis. Pancytopenia was effectively treated with corticosteroids. Re-examination of the bone marrow confirmed a recovery of normal hematopoietic cells with a infiltration of many macrophages. It is strongly suspected that the bone marrow necrosis in this case could be associated with a bone marrow suppression due to FeLV infection. 相似文献
8.
Fumihiko OKUMURA Takeshi SHIMOGIRI Kotaro KAWABE Shin OKAMOTO Masahide NISHIBORI Yoshio YAMAMOTO Yoshizane MAEDA 《Animal Science Journal》2006,77(2):188-195
The gene constitution of polymorphisms of the four calpain genes (µ‐calpain, m‐calpain, p94, and µ/m‐calpain) were analyzed in South‐East Asian native chickens, White Leghorn and Broiler commercial chickens, and Red and Green jungle fowl. Polymorphisms were detected at all loci in chickens and Red jungle fowl, but only for CAPN1 (µ‐calpain gene) in Green jungle fowl. CAPN2 and CAPN1.5 are linked on chicken chromosome 3, and the genotype for these loci were treated as haplotype. Some combinations of calpain loci were tested using principal component analysis, and the best combination (CAPN1, CAPN3, and CAPN1.5) was determined. The proportion of polymorphic loci (Ppoly) and heterozygosity (H?) were 1.00 and 0.316–0.465 in domestic chickens and red jungle fowl, and 0.33 and 0.137 in Green jungle fowl, respectively. GST values suggested that the degree of subdivision among native chickens was relatively low except for Thailand, which was highest. Pair‐wise FST testing, dendrogram and principal component analysis from the results of calpain loci showed that the four South‐East Asian native and commercial chicken populations were close genetically. 相似文献
9.
Spatially distributed morphological characteristics of macropores in forest soils of Hitachi Ohta Experimental Watershed, Japan 总被引:1,自引:0,他引:1
Shoji Noguchi Yoshio Tsuboyama Roy C. Sidle Ikuhiro Hosoda 《Journal of Forest Research》1997,2(4):207-215
Morphological characteristics of macropores in forest soil profiles were investigated at Hitachi Ohta Experimental Watershed
in Japan. Nine individual profiles at different locations (various spatial scales in a catchment) and twenty profiles at one
site (a small spatial scale) were excavated to the bedrock to investigate density, origin, diameter, direction, and gradient
of macropores. Macropore densities in a soil profile ranged from 3.5 to 29.1 per m and from 5.4 to 75.1 per m2, respectively. Subsurface erosion, root channels, and interactions between subsurface erosion and root channels accounted
for 36.9, 36.5, and 19.0%, of the described macropores. The mean macropore diameter in organic-rich soil layer (17–20 mm)
was larger than in the B horizon (11–14 mm) at both spatial scales. The dominant gradients of all macropores in the organic-rich
soil layer and B horizon were at negative oblique angles. Approximately 90% of the macropores in the organic-rich soil layer
and approximately 80% of the macropores in the B horizon fell within the range between −50 and 50 degree planar direction.
Subsurface flow and root systems are believed to play important roles in determining the morphological characteristics of
macropores. These characteristics appear to have variable influences in different soil horizons rather than at different spatial
scales.
A part of this paper was presented at the 103th (1992) and 105th (1994) Annual Meetings of Japanese Forestry Society. 相似文献
10.
Kazuya KUSHIDA Urs GIGER Toshihiko TSUTSUI Megumi INABA Yoshio KONNO Kureha HAYASHI Kana NOGUCHI Akira YABUKI Keijiro MIZUKAMI Moeko KOHYAMA Yasuyuki ENDO Osamu YAMATO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(6):743-746
Erythrocyte pyruvate kinase (PK) deficiency is an inherited glycolytic erythroenzymopathy
caused by mutations of the PKLR gene. A causative mutation of the feline
PKLR gene was originally identified in Abyssinian and Somali cats in
the U.S.A. In the present study, a TaqMan probe-based real-time PCR genotyping assay was
developed and evaluated for rapid genotyping and large-scale screening for this mutation.
Furthermore, a genotyping survey was carried out in a population of four popular purebred
cats in Japan to determine the current mutant allele frequency. The assay clearly
displayed all genotypes of feline PK deficiency, indicating its suitability for
large-scale survey as well as diagnosis. The survey demonstrated that the mutant allele
frequency in Abyssinian and Somali cats was high enough to warrant measures to control and
prevent the disease. The mutant allele frequency was relatively low in Bengal and American
Shorthair cats; however, the testing should still be carried out to prevent the spread of
the disease. In addition, PK deficiency should always be considered in the differential
diagnosis of anemia in purebred cats in Japan as well as worldwide. 相似文献