• Archives of Pharmacal Research
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• 제20권4호
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• pp.358-362
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• 1997

Metabolite identification and urinary and biliary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1 -piperazinyl)-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid, hydrochloride] after oral administration have been studied in Sprague-Dawley rats. The excretion kinetics were monoexponential. Most of the drug was eliminated via the hepatic and renal routes. Mean renal clearance of DW116 was 73.4 ml/hr/kg and mean biliary clearance was 83.8 ml/hr/kg. The major metabolite excreted in the bile was identified as the glucuronide ester of the parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound, $^{19}$ F-NMR and LC-MS methods. The glucuronide conjugate was also found in urine. The mean urinary recoveries of free and total (free plus glucuronide ester) DW116 were $28.6{\pm}2.7% $and $36.4{\pm}1.8%$ of the administered dose and the corresponding biliary recoveries were $14.4{\pm} 5.5%$ and $37.0{\pm}7.6%$, respectively.

• Archives of Pharmacal Research
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• 제9권1호
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• pp.49-54
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• 1986

Effect of sodium taurodeoxycholate (TDC) infused intravenously on the pharmacokinetics of methylene blue (MB) was studied in the rat to investigate the role of ion-pair complexation in the body on drug elimination and disposition. Distribution volume (Vd) of MB was increased significantly (p< 0.05) by TDC infusion. Considering together with the fact that apparent partition coefficient (APC) of MB between phosphate buffer (pH 7.4) and n-octanol was increased markedly by TDC, the increase in Vd seemed to be the result of decreased polarity of MB by ion-pair formation with TDC. But total body clearance (CLt) and biliary excretion clearance (CLbil) of MB were not increased significantly by TDC.

• 한국응용과학기술학회지
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• 제3권1호
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• pp.49-55
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• 1986

The purpose of the study was to find an effect of Medium Chain Triglycerids (MCT) diet on cholesterol metabolism in rat. Sprague-Dawley rats were fed two different diets containing MCT(trioctanoate) and corn oil respectively. After feeding to each group for four weeks, the levels of serum and liver cholesterol, the excretion rates of fecal and biliary steroids, and also bile acid composition were investigated. The results obtained from the study are as follows : (1) The average body weight gain in MCT group was almost same as that in the corn oil group. (2) The concentration of serum cholesterol in MCT group was lower than that in the corn oil group. Therefore it is confirmed that the cholesterol lowing action of MCT diet was practically high. (3) The concentrations of liver cholesterol and Triglyceride in MCT group were almost same as that in the corn oil group. Therefore it is thought that the level of liver lipids was not influenced by the difference of diet in this study. (4) The excretion rate of fecal neutral steroid in MCT group was significantly lower than that in the corn oil group, while the rate of fecal bile acid excretion was about same in both MCT and corn oil group. (5) The composition rates of fecal bile acid such as cholic acid, chenodeoxycholic acid and deoxycholic acid, a secondary acid of cholic acid, in MCT group were significantly lower than that in the corn oil group. (6) The excretion rates of biliary cholesterol and bile acid in MCT group were significantly higher than that in the corn oil group, while the composition rates of biliary bile acid such as chenoddeoxycholic acid and deoxycholic acid in MCT group were significantly higher than that in the corn oil group.

• Preventive Nutrition and Food Science
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• 제2권1호
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• pp.35-41
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• 1997

The pancreas is an important organ in the maintenance of zinc homeostasis. Endogenous zinc is con-tinuously secreted via pancreatic exocrine fluid or to a lesser extent in bile. Much of the endogenous secretion must be reabsorbed to sustain zinc homeostasis. The objective of this study was to estimate the relative size of the pancreatic/biliary zinc pool in comparision to the dietary zinc intake, and to study the effect of the phytate and calcium on the zinc homeostasis using a rat model. At the termination of the experiment, pan-creatic/biliary fluid was collected from the rats. Both radioactivity and total zinc were measured and the relative size of the pancreatic/biliary zinc pool was estimated. To determine the effect of phytate and calcium on zinc homeostsis, dietary zinc intake, the amount of zinc in pancreatic.biliary fluid and fecal zinc excretion were measured. The flow rate of pancreatic/biliary fluid, as corrected for tubing constriction, gives the corrected zinc concentration in the pancreatic/biliary fluid was 2.2 times higher than dietary zinc intake. To maintain zinc homeostasis, zinc absorption/reabsorption was very efficient in the current model; 76%, 88% of absorption/reabsorption for low calcium group and high calcium group 81% for phytate group and non-phytate group, respectively.

• The Korean Journal of Physiology
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• 제5권2호
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• pp.45-54
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• 1971

That different mechanisms are involved in the secretory processes by the liver and the kidney of various dyes has been indicated by Sporter (1959), Kim and Hong (1963). Andrews (1958). suggested that a striking difference in the dye-secretory mechanism existed even in the same organ from species to species. Hence, the attempt has been made to study in the rabbit the secretory processes by the live. and the kidney of either phenol red (PSP), bromsulfalein (BSP) or green in the presence of Na-acetate, Na-taurocholate, P-Aminohippurate (PAH) or Benemid. In 37 rabbits, weighing about 2kg., anesthetized with ether, a dye was administered in such 8 manner that the plasma concentration was kept at a relatively constant level throughout the whole experimental period. Hepatic bile sad urine samples were quantitatively collected through the canulae which were previously inserted into the common bile duct (with the cystic duct ligated) and the urinary bladder, respectively, while arterial samples were taken from a femoral artery. After 50 min from the onset of dye administration, these samples were obtained every 10 mit for a period of 40 min. This was followed by the administration of either Na-acetate, Na-tauro-cholate, PAH or Benemid with a repetition of the same sample collecting procedures just stated. The results may be summarized as follows: 1) Na·acetate augmented urinary clearance of PSP by nearly 300 per cent, but lowered urinary BSP clearance by about 50 per cent. It enhanced biliary BSP clearance by 40% and had no effect on biliary psp clearance. 2) Na-taurocholate lowered biliary and urinary clearance of PSP by 10 per cent and 30 per cent respectively, and had no effect on both biliary and urinary clearance of BSP. 3) PAH lowered both biliary and urinary excretion of BSP and PSP, while it lowered the biliary excretion of indocyanine green which was excreted only in the bile. 4) Benemid suppressed BSP excretion by the liver and the kidney. 5) raper chromatographic analysis of PSP and of BSP in the bile and urine samples gave the following results: a) PSP Ivas excreted in the urine and bile only in free forms, and no modification in the excretory pattern was brought about by Na-taurocholate. b) BSP was excreted in the urine in 4 different conjugated froms and in the bile in both 3 different conjugated forms and in a free form. Na-taurocholate modified the excretory pattern of the urinary BSP.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.422.2-423
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• 2002

The purpose of the present study was to investigate the hepatic uptake and biliary excretion of IH-901. a potential anticancer agents. in rats. IH-901 was mainly distributed into the liver after its iv administration at the dose of 10-30 mg/kg. The liver concentration of IH-901 at 7 min after its Iv administration was comparable with its initial concentration of the plasma. Moreover. recovery ratio of IH-901 in the bile for 6 hr was more than 40% after its iv administration. (omitted)

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.160-165
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• 1993

The effects of Glycyrrhizae Radix (GR) on the metabolism of acetaminophen (AA) were examined in male Sprague-Dawley rats. The methanol extract of GR (500 mg/kg) was administered orally to rats for 6 days. AA and its metabolites excreted in bile, urine and blood within 120 min after dosing of AA (150 mg/kg, i.v.) were assayed by HPLC. Treatment of rats with the methanol extract of GR significantly increased the cumulative biliary excretion of AA-glucuronide (156% of the control) and decreased that of AA-sulfate (63% of the control). The cumulative urinary excretion of AA-glucuronide was also significantly increased to 132% of the control. GR treatment significantly increased total (biliary plus urinary) excretion of AA-glucuronide (172% of the control) without influencing thioether and sulfate conjugates of AA. The results clearly show that GR enhances UDP-glucuronosyl transferase-mediated detoxication of AA, but may not influence sulfotrans-ferase-mediated and cytochrome P-450-mediated metabolites formation.

• 대한약리학회지
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• 제12권2호
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• pp.51-59
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• 1976

Methylene bis (3, 4, 6-trichlorophenoxy acetic acid) 'MTPA' has been developed for the purpose of treatment of clonorchiasis. It has been rpeorted that, in patients treated with MTPA, the flukes in the liver were killed, elevated serum bilirubin returned to normal and the patients´ general condition was improved. However it took $1{\sim}4 $ weeks to obtain sufficient therapeutic effects. In rabbits, excretion of bilirubin in the bile was increased by the MTPA, and this action was enhanced by a combination of deoxycholic acid with MTPA. This study was designed as a part of a series to increase the therapeutic effect of MTPA, by observing the relation of the blood level of MTPA with the excretion of MTPA in the bile, and the excretion of MTPA with bilirubin excretion in the bile caused by the injection of MTPA alone or in combination with deoxycholic acid. $^{14}C-labeled$ MTPA alone or with deoxycholic acid were injected into the ear veins of rabbits. The amout of bile, MTPA and bilirubin in the bile and the blood level of MTPA were measured. The results obtained were as follows: 1. The amount of excreted bile was decreased gradually as the time elapsed in both groups, that is groups injected with MTPA alone and with deoxycholic acid, without any significant difference between either group. 2. The largest amount of MTPA excretion in the early stage of the MTPA excretion in both groups, but deoxycholic acid caused an increase in blood level of MTPA whereas biliary excretion of MTPA decreased, especially in the early stage after drug injection. 3. The significant increment of bilirubin excretion began within an hour and it reached peak level in $2{\sim}2\frac{1}{2}$ hours after drug injection in both groups, but the amount of excreted bilirubin was larger in the combined group. The above results suggest that deoxycholic acid interferes with the biliary excretion of MTPA, and that there is no close relation between the increased excretion of MTPA and bilirubin excretion. But there is a close relation between blood level or tissue concentration of MTPA and bilirubin excretion. Concerning the influence of deoxycholic acid on the therapeutic effect of MTPA, deoxycholic acid would enhance the effect of MTPA, if the parasites take the drug from the blood, but diminish its effectiveness if they take the drug from the bile.

• Journal of Pharmaceutical Investigation
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• 제22권1호
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• pp.11-21
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• 1992

The effects of colchicine on the plasma elimination and biliary excretion of various organic anions in rats were examined. Elimination of indocyanine green (ICG) or rose bengal (RB) from plasma was significantly delayed when rats were treated with colchicine (3 mg/kg body weight) 3 hr prior to the administration of the dye. On the other hand, disappearance of sulfobromophthalein (BSP) or bromophenol blue (BPB) from plasma was not influenced by colchicine. The plasma disappearance and biliary excretion of organic anions were kinetically analyzed based on a compartment model, in which the deep compartment and the unknown disposition are incorporated. The transfer rate constants of ICG or RB, $k_{23}$ (from the liver to the deep compartment) and $k_{3B}$ (from the deep compartment to the bile), were decreased by colchicine, but those of BSP or BPB were not changed. A mechanism for the decrease in the $k_{23}$ and $k_{3B}$ values for ICG and RB might be explained by a inhibition of colchicine to the intracellular cytoskeleton. The hepatocellular distribution of RB or BPB was then determined. BPB mainly distributed to the cytosolic fraction, but RB distributed to each hepatocyte organelle. Taken together. it was suggested that ICG or RB is transported through hepatocytes into bile with the aid of the cytoskeleton, whereas BSP or BPB is handled by hepatocytes in a different way.

• 약학회지
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• 제36권1호
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• pp.26-36
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• 1992

The metabolic profile of triprolidine, 2-[1-(4-methylphenyl)-3-(1-pyrrolidinyl-1-propenyl)] pyridine, was determined in rat urine and bile. The free fractions of urinary and biliary extracts were obtained without hydrolysis, and the conjugated fractions of extracts were obtained with enzyme hydrolysis using ${\beta}-glucuronidase$ from Escherichia coli. The mixture of N-methyl-N-trimethylsilyltrifluoroacetamide/trimethylsilyl chloride (100 : 1, v/v) was used to derivatize the extracts and then analyzed by gas chromatography/mass spectrometry. Hydroxymethyltriprolidine, hydroxytriprolidine, triprolidine carboxylic acid, dihydroxytriprolidine 1, dihydroxytriprolidine 2, oxotriprolidine carboxylic acid and unchanged triprolidine were detected in rat urine and bile, which were obtained after oral treatment with triprolidine hydrochloride. The maximum urinary excretion rate of triprolidine and hydroxymethyltriprolidine which were extracted from free fraction was at 1 to 2 hours after drug administration. Hydroxymethyltriprolidine was detected in conjugated fraction, and the maximum urinary excretion rate of that metabolite was at 2 to 3 hours in rat. In rat bile analysis, triprolidine was detected only in free fraction and its biliary excretion rate showed the maximum within 30 minutes after drug administration and decreased continuously thereafter. The excretion percentage of triprolidine and hydroxymethyltriprolidine to the initial dose of the parent drug in bile and urine of rats were all low.