• The Korean Journal of Pharmacology
• /
• v.12 no.2 s.20
• /
• pp.51-59
• /
• 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 Nutrition and Health
• /
• v.31 no.9
• /
• pp.1394-1403
• /
• 1998

The study was designed to observe the effect of dietary calcium and fats on plasma cholesterol level, hepatic microsomal fluidity and HMG-CoA reductase activity as well as the excretion of fecal bile acids and neutral sterols in 1, 2-dimethylhydrazine(DMH)-treated rats. Male Sprague Dawley rats, at 7 weeks of age, were divided into 2 groups, 0.3% and 1.0% Ca levels and each group again subdivided into 2 groups of corn oil and perilla oil. Each rat was intramuscularly infused with DMH for 6 weeks to give total dose of 180mg/kg body weight and also fed experimental diet containing 15%(w/w) different fit and Ca(0.3% or 1.0%) for 20 weeks. High dietary calcium(1.0%) did not significantly influence on plasma cholesterol as well as hepatic microsomal fluidity and HMG CoA reductase activity, but significantly reduced the excretion of total bile acid per gram of faces and increased the excretion of total neutral sterol. However, high dietary Ca reduced the excretion of secondary bile acid(deoxycholic and lithocholic acids) which was known as promoter for colon cancer. Perilla oil rich in n-3 ${\alpha}$-linolenic acid significantly decreased plasma cholesterol by increasing hepatic microsomal fluidity compared with corn oil, but did not influence on HMG CoA reductase activity. Perilla oil did not influence on fecal excretion of total and primary bile acids, but reduced the excretion of secondary bile acids. Therefore, it could be recommended to consume more fish product and food rich in calcium and use more perilla oil in meal preparation to prevent from coronary hear disease and colon cancer especially when high fit diet has been practiced. (Korean Nutrition 31(9) : 1394-1403, 1998)

• Journal of Pharmaceutical Investigation
• /
• v.7 no.1_4
• /
• pp.38-50
• /
• 1977

A study on the mechanism of biliary and urinary excretion of chloramphenicol has been performed in the dog. 1) Chloramphenicol administered intravenously to dogs with ligated renal pedicle, readily appeared in bile greater than in plasma. 6.9% of a 50mg /kg i. v. dose of chloramphenicol were excreted into bile within 100 minutes. During the same periods of above experiment, the bile/plasma concentration ratios(B/P ratios) were 46 to 87. 2) Chloramphenicol injected into the vein of dog was rapidly excreted into urine. 18% of the administered dose were excreted into urine within 70 minutes. In the same periods of this experiment, Ccm/Ccr ratios were greater than 1.0 in most cases. 3) In experiment of simultaneous measurement of biliary and urinary excretion of chloramphenicol, Ccm/Ccr ratios were less than 1.0 and B/P ratios were 50 to 52. 4) In experiment measured simultaneously biliary and urinary excretion both Ccm/Ccr and $C^Hcm$(hepatic clearance) were significantly declined by probenecid, but not affected by 2,4-DNP and aminophylline although 2,4-DNP increased only bile flow and aminophylline both bile and urine volume. 5) Ccm/Ccr and $C^Hcm$ were increased in proportion to increment of plasma concentration ranging from 3.3 to 30 mg% of chloramphenicol. But when plasma concentration were increased to 70mg %, Ccm/Ccr were not increased and $C_Hcm$ were reduced about 30% in comparison with values obtajned at 30mg% of chloramphenicol. 6) Free/Bound(free to bouid from) ratios ranging from 1.0 to 90.0mg% of chloramphenicol were 76.2+3.72% $(mean{\pm}S.E.)$ Above results suggest that chloramphenicol is excreted into bile by a process of active trasport, that excretion of chloramphenicol into urine was made up with dual process, reabsorption and secretion, and that renal secretion was attained by active trasport process although renal reabsorption process could not understand.

• YAKHAK HOEJI
• /
• v.36 no.1
• /
• pp.26-36
• /
• 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.

• Journal of Pharmaceutical Investigation
• /
• v.7 no.1_4
• /
• pp.13-21
• /
• 1977

This study on the biliary excretion of sulfadiazine has been established in the rats. 1. Sulfadiazine, administered intravenously to rats with ligated renal pedicles and a cannulated bile duct, rapidly appeared in the bile in high concentration. 2. Between 0-30min. and 30-60 min. after administration, the bile-to-plasma concentration ratios(B/P) of the sulfadiazine were 1. 02-2.67, 1.14-3.79 for 1mg/kg dose, 1.48-3.89, 1.30-3.81 for 10mg/kg, 1.97-4.27, 2.11-4.07 for 50mg/kg, and 1.70-4.21, 1.71-5.34 for 100mg/kg. Thus, B/P ratios at any doses of sulfadiazine greatly exceeded 1.0 at all experimental periods. 3. Furthermore, the biliary excretion of sulfadiazine was inhibited by probenecid significantly. 4. Hepatic clearance of sulfadiazine in the rats was increased from 0.515 to 1.780 ml/60 min. when the dose was raised from 1.0mg/kg to 50.0mg/kg of sulfadiazine, but at 100mg/kg, decreased to 1.250ml/60min. All these results indicate that sulfadiazine is excreted into the bile by active transport process in the rats with ligated renal pedicles and a cannulated bile duct.

• Archives of Pharmacal Research
• /
• v.9 no.1
• /
• pp.49-54
• /
• 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.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.26 no.5
• /
• pp.927-935
• /
• 1997

This study was conducted to investigate the effect of nondigestable substances and calcium such as oligosaccharide, agar, saponin, tannin and calcium on the reduction of lipid status in rats fed high fat diet. In order to make the observation, the lipid content in plasma, liver and the feces, and bile acid excretion were measured of r 4 weeks. the results obtained from this research are as follows. Concentration of total lipid in plasma seemed highest in the control group and were significantly lower in groups oil-gosaccharide, agar and calcium-tannin, compared to the control group. Concentration of total cholesterol in plasma was significantly lower in groups oligosaccharide, agar, calcium and calcium-saponin, compared to the control group. The improvement in lipid status seems to be insignificant with oligosaccharide, showed increase in total bile acids excretion in feces and decrease in total cholesterol in plasma, compared to the control group. These evidence seems to indicate improvement of the plasma lipid status by calcium and agar supplementation.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.27 no.1
• /
• pp.126-131
• /
• 1998

This study was undertaken to determine the effect of yellow and black soybeans on plasma and hepatic lipid composition and fecal lipid excretion in Sprague Dawley rats. Animals were fed with diets containing 52% yellow soybean, 50% black soybean, or 20% casein for 7 weeks. Feeding efficiency was significantly increased in the animals fed soybeans(p<0.05). Plasma cholesterol concentration was significantly lowered in the group fed yellow soybean compared with black soybean and casein-fed control (p<0.05). Hepatic triglyceride concentration was significantly lowered in soybean groups compared with casein-fed control(p<0.05), whereas hepatic cholesterol concentration was not affected by diet treatments. Soybean feeding significantly increased fecal weight, triglyceride and bile acid contents compared with casein feeding(p<0.05). It is concluded that soybean feeding in rats affects plasma and hepatic lipid levels by increasing the excretion of triglyceride and bile acids.

• Journal of the Korean Applied Science and Technology
• /
• v.3 no.1
• /
• pp.49-55
• /
• 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.19 no.1
• /
• pp.1-11
• /
• 2016

Cholestasis results from impairment in the excretion of bile, which may be due to mechanical obstruction of bile flow or impairment of excretion of bile components into the bile canaliculus. When present, cholestasis warrants prompt diagnosis and treatment. The differential diagnosis of cholestasis beyond the neonatal period is broad and includes congenital and acquired etiologies. It is imperative that the clinician differentiates between intrahepatic and extrahepatic origin of cholestasis. Treatment may be supportive or curative and depends on the etiology. Recent literature shows that optimal nutritional and medical support also plays an integral role in the management of pediatric patients with chronic cholestasis. This review will provide a broad overview of the pathophysiology, diagnostic approach, and management of cholestasis beyond the neonatal and infancy periods.