• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.171-178
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• 2000

To evaluate the pharmacokinetic properties and tissue distribution of a newly developed recombinant human erythropoietin (GC-rhEPO), we analyzed the plasma and tissue levels of erythropoietin by an ELISA after intravenous (IV) and subcutaneous (SC) adminstration to the male rats at the doses of 20, 100, 500 or 2,500 unit/kg. After single IV bolus injection of GC-rhEPO, the plasma concentration was rapidly increased and decreased with two phases with half-lives of 13.4 min and 2.94 hours. AUC was increased dose- dependently but plasma half-lives remained constant regardless of GC-rhEPO doses. Following SC administration, the plasma concentration increased slowly with half-life of 9.2 hours and reached peak at 8 hours. Mean residence time and bioavailability were 18.2 hours and 44%, respectively. After single IV dose of 100 unit/kg, tissue GC-rhEPO level was higher in bone marrow and spleen, while the depletion rate was slower in liver and bone marrow, indicating the higher affinity of GC-rhEPO to bone marrow. Taken together, the experimental results indicate that GC-rhEPO contained the typical pharmacokinetic properties and the tissue distribution patterns inherent to human erythropoietin.

• Archives of Pharmacal Research
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• v.19 no.5
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• pp.359-367
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• 1996

The pharmacokinetics of LB20304 was investigated following intravenous (IV) and oral administration to rats and dogs. Additionally, in vitro metabolism and serum protein binding studies were also conducted. The total body clearance, apparent volume of distribution, terminal half-life, and extent of bioavailability were 21.8 ml/min/kg, 2265 ml/kg, 93.6 min, and 30.8% for rats; and 7.95 ml/min/kg, 4144 ml/kg, 363 min, and 81.1% for dogs, respectively. LB20304 was stable in the liver microsome containing NADPH generating system and its serum protein binding was 58.5-65.8% for rats, 19.1-29.6% for dogs, and 56.9-59.6% for humans. Its tissue concentration levels in lever, stomach, small intestine, and kidney were 9.5 to 26.1 times greater than plasma level, but the concentration in testis was quite low and that in brain was negligible in rats. The 48 hr urinary recovery of the dose was 44% for IV dosing and 14% for oral dosing, shereas the 48 hr biliary recovery of the dose was 6.4% for IV dosing and 4.5% for oral dosing in rats. In summary, the pharmacokinetic properties of LB20304 were characterized by its good oral absorption, long plasma half-life, and good tissue distribution.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.28-34
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• 1993

Using in vitro autoradiography with a digital autoradiography system and radioreceptor assay, the distribution and the binding characteristics of the muscarinic cholinergic receptors (mAChR) were studied in regions of rat brain. Radioreceptor assay revealed that mAChR could be measured with saturation binding assay in the brain and heart homogenates: No difference in Kd or Bmax of the brain or heart was found between the normal Wistar rats and SHR rats. Specific binding of $^3H$ quinuclidinyl benzilate (QNB) increased and saturation was reached by 2 hours after incubation with slide-mounted brain tissue. The distribution of mAChR was heterogeneous along the fields of brain. Affinity (Kd) of mAChR was not different significantly among cortex, hippocampus and caudate-putamen. No difference was found between normal rats and SHR strain. More receptors (Bmax) were found in the cortex and hippocampus than in the caudate-putamen in normal rats. More receptors were found in the cortex and caudate-putamen in SHR rats than in normal rats. Radioreceptor assay and digital autoradiographic analysis of affinity and number of mAChR gave the same results. With the above findings, we concluded that we could use digital autoradiographic system with $^3H$-QNB in the characterization of mAChR of rats and that the cortex and caudate-putamen of SHR strain rats have more receptors than those of normal rats.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.223-230
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• 1995

The phannacokinetics and tissue distribution of DWQ-013, a new quinolone, were examined in rats and mice following a single intravenous and oral administration. DWQ-013 in plasma and urine was determined by both HPLC and microbiological assay. The plasma concentration of the drug declined biexponentially. The terminal half life of the drug was 11.11$\pm$0.14 hour after intravenous dosing. The volume of distribution at terminal elimination phase(Vd$_\beta$) and total clearance of the drug were 1.29$\pm$0.15 l/kg and 0.78$\pm$0.09 l/h/kg. The bioavailability of DWQ-013 after oral administration was 56.0% (HPLC) and 77.2%(bioassay), respectively. Twelve-hour urinary recovery of drug was measured by HPLC and bioassay to 0.035$\pm$0009% and 4.71$\pm$066% after oral dosing, to 0.055$\pm$0.014% and 7.65$\pm$1.53% after intravenous dosing, which may indicate the presence of biologically active metabolites. Binding of the drug to plasma proteins ranged from 97%~99% at various concentrations. The drug was highly distributed in order of liver, kidney and lung after 1.5 hours in mice.

• Preventive Nutrition and Food Science
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• v.2 no.3
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• pp.219-224
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• 1997

The pancreas is an important organ in the maintenance of zine homeostasis. The pancreatic tissue used in this study was obtained from rats fed varying levels of dietary Ca nd phytate followed by intraperitoneal {TEX}${65}^Zn${/TEX} injection. THe objective of this study was to determine the molecular size and distribution of compounds that may represent zinc-binding complexes in pancreatic tissue homogenates. The supernatant of the homogenized pancreatic tissue was separated using a Sephadex G-75 column with Tris buffer at pH 8.1. All subfractions were assayed for zinc, protein and {TEX}${65}^Zn${/TEX} activity. The elution of subfractions from pancreatic tissue homogenates showed a prominent peak corresponding to the high molecular weight protein standard (>66kd). A sall molecular weigth protein (<6.5kd), that was absorbed at 280nm, was also present: prominently in low Ca group, however not much as in high Ca group. These small compounds may combine weakly with zinc in pancreatic tissue an serve as zinc-binding ligands in pancreatic/biliary fluid. In the duodenum, these ligands dissociate zinc into an ionic form which becomes vulnerable to phytate complexation.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.419-425
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• 1997

The pharmacokinetics of DWP20364 (1-cyclopropyl -5-amino-6,8-difluoro-7-(2,7-diazabiclo [3,3,0] oct-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone containing C7-bicyc-talc structure, were compared with those of ciprofloxacin (CPFX) after single intravenous (i.v.) and oral (p.o.) administration to rats using microbiological assay (bioassay). After i.v. administration to rats, the plasma concentrations of the two drugs declined biexponentially. The terminal half-lives (t$_{1}$2$\beta$/) of DWP20364 were 110$\pm$ 13.2 min and 117$\pm$3.09 min after i.v. and p.o. administration, respectively, and they were significantly higher than those of CPFX (45.5$\pm$9.52 min and 48.3$\pm$ 12.1 min, respectively). Similar results were also obtained from plasma concentrations and area under the plasma concentration-time curves. The total body clearance of DWP20364, 7.82$\pm$0.37 ml/min/kg was significantly slower than that of CPFX, 27.3 $\pm$ 11.1 m1/ min/kg. Above data suggested that the antimicrobial activity of DWP20364 could be longer than that of CPFX. The urinary recovery after i.v. and p.o. administration of DWP20364 was significantly lower than those of CPFX suggesting that the effect of DWP20364 on urinary tract infection could be lower than that of CPFX. The serum protein binding values of DWP20364 at 2$\mu$g/ml were apparently 91.5~93.1% in rats and human. DWP20364 was distributed by the order of liver, lung, kidney, sf)leon, heart, muscle and brain collected at 30 min after orally administered.

• Journal of Environmental Health Sciences
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• v.23 no.1
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• pp.8-13
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• 1997

Distribution and persistence of fenitrothion in rats were studied following oral administration of a single dose 300 mg/kg of body weight. Residue of the parent compound was analyzed in blood, liver, kidney, brain, lung and heart 2, 4, 6, 8 hours and 1, 2, 3, 5, 7 days after oral administration. The maximum concentration of fenitrothion appeared in the blood, kidney, heart on the 2 hour and liver, brain, lung on the 4 hour. Residues of the parent compound in kidney were much higher and persistent than other tissues and the pesticide was not detected on the 7th day. Recoveries were ranged from 83.0(lung, $1 \mu g/g$) to 97.5%(blood, $1.5 \mu g/ml$).

• The Journal of the Korean dental association
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• v.15 no.4
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• pp.285-288
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• 1977

The purpose of the current study was to evaluate the effect of the zinc-deficient diet on the connectine tissue of oral mucosa in the albino rats. The zinc dificient diets were supplied to the rats for 4 weeks. The results were as follows: Most of the papillas of lamina prmina propria were shortened. The abnormal distribution and orientation of the fibrous elements were observed. The stain ability of fihrous elements in the Mallory azan stain was decreased. The amorphous intercellular substance showed slight metachromasia in the toluichine blue stain and low PAS reactinity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.818-823
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• 2011

Recently, we showed that green tea extract (GTE) markedly lowers the intestinal absorption of $^{14}C$-benzo[a]pyrene ($^{14}C$-BaP) and enhances its secretion into the biliary route, suggesting a protective role for GTE against body burden. These findings indicate that green tea could be used as an effective dietary means against the toxicity of BaP. The present study, therefore, was designed to investigate if green tea intake could affect the tissue distribution and deposition of $^{14}C$-BaP in rats. Male Sprague-Dawley rats had free access to a nutritionally adequate AIN-93G diet and deionized water. At ~340 g of weight, the rats were injected intraperitoneally with 27.4 kBq of [4-$^{14}C$]-BaP and 5.0 mg of BaP dissolved in $300\;{\mu}L$ of olive oil and then assigned randomly to the following two groups: one group (GTE) of rats was fed the AIN-93G diet with GTE via drinking water at approx. 4.7 mg of catechins/d, whereas the other was fed the same diet but without GTE (control). At 4 wk of dietary treatment with GTE, animals were euthanized and heart, liver, brain, spleen, kidney, retroperitoneal fat, testis, and epididymal fat were collected, weighed, and analyzed for tissue $^{14}C$-BaP. Both the control and GTE groups continuously gained weight throughout the study, but there was no significant difference between the groups. No significant differences were observed in the weights of heart, liver, brain, spleen, kidney, retroperitoneal fat, testis, and epididymal fat. However, the radioactivities of $^{14}C$-BaP, expressed in dpm/g, were significantly lower in the heart, liver, brain, spleen, and epididymal fat of rats receiving GTE as compared to their respective controls. These data indicate that green tea intake markedly lowers tissue accumulation of $^{14}C$-BaP. Taken together, these findings suggest that the decreased tissue levels of BaP by GTE intake may be associated with lowered intestinal absorption of BaP and its enhanced secretion into the bile.

• Preventive Nutrition and Food Science
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• v.15 no.1
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• pp.1-6
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• 2010

The effect on body fat accumulation on male Wistar rats undergoing continuous feeding with a histidine-enriched diet was investigated. Five-week-age rats were assigned to two groups and were fed either the control diet (purified diet AIN-$76^{TM}$) or the histidine-enriched diet containing 3% histidine for 28 days. It was observed that both adipose tissue masses in retroperitoneal and epididymal areas of rats fed histidine-enriched diet significantly decreased (p<0.05) compared to those of control rats, while there was no significant difference in the food efficiency ratio between them. The blood levels of histidine derivatives of 3-methylhistidine and carnosine were significantly (p<0.05) increased in the rats fed a histidine-enriched diet, whereas there were no significant different between the histidine-enriched diet and control groups in the general amino acid distribution. Our results demonstrate that a histidine-enriched diet suppresses body fat accumulation in rats.