• YAKHAK HOEJI
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• v.27 no.2
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• pp.133-138
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• 1983

The interaction between nalidixic acid and probenecid was studied pharmacokinetically in rabbits. The blood level and the area under the concentration curve(AUC) of nalidixic acid administered orally in dose of 100mg/kg was elevated by the coadministration of probenecid. Probenecid inhibited both the urinary excretion and the biliary excretion of nalidixic acid. Therefore, biological half-life of nalidixic acid was prolonged by the coadministrarion of probenecid. It was considered that the coadmini-stration of probenecid is more desirable than the single administration of nalidixic acid for the therapeutic effect.

• Journal of Pharmaceutical Investigation
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• v.13 no.2
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• pp.51-58
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• 1983

In order to elucidate the effects of Panax Ginseng on the pharmacokinetic parameters of nalidixic acid in a patho-physiological changes, the kinetics of the disappearance of the drug from the blood, appearance in the bile and urinary excretion were studied in $CCl_4-toxicated$ rabbits. The pharmacokinetics of the drug nalidixic acid in rabbits were modeled by a two compartment. Total saponin, water extract from Panax Ginseng, significantly decreased biliary and urinary excretion of nalidixic acid.

• Journal of Pharmaceutical Investigation
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• v.27 no.2
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• pp.109-117
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• 1997

In order to elucidate the effect of phenobarbital (PB) on the nonlinear pharmacokinetic behavior of naproxen (NAP), we compared the dose dependent hepatic intrinsic clearance, biliary excretion and protein binding of NAP in control rats to those in the PB-pretreated rats which were intraperitoneally pretreated with PB sodium (75 mg/kg) once a day for four days. NAP was injected via femoral (1.5 mg/kg) and portal(0.25, 0.5, 1.5, 15 and 30 mg/kg) vein to the control and PB-pretreated rats, respectively. And also, we measured the plasma free fraction of NAP with the equilibrium dialysis method and the biliary excreted total amounts of NAP in both rats. Plasma free fraction of NAP was decreased in lower concentration than $150\;{\mu}g/ml$ of NAP due to PB pretreatment. In higher concentration, however, plasma free fraction was increased. These in vitro results suggest that the total protein concentration was increased but the total binding capacity of NAP to protein was decreased by PB-pretreatment. The total plasma clearance and the hepatic intrinsic clearance of NAP had similar values in both groups, respectively. And, both clearances of NAP were significantly increased by PB-pretreatment. Even though the plasma free fractions of NAP in both groups were constantly remained within the concentration range according to the increase of administration dose, the hepatic intrinsic clearances of NAP were significantly increased in both groups with the increased dose. And, the biliary excreted total amounts of NAP were significantly increased by PB-pretreatment at the lower dose, but decreased at the higher dose. These in vivo results suggest that NAP represents the uncommon nonlinear pharmacokinetic behavior that the hepatic intrinsic clearance was enhanced with the increased dose, and that PB enhances further the hepatic intrinsic clearance of NAP with the increased dose due to its enzyme induction effect.

• Advances in pediatric surgery
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• v.3 no.1
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• pp.6-14
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• 1997

To differentiate biliary atresia from intraheaptic cholestasis, Tc-99m DlSIDA hepatobiliary scintigraphies and percutaneous needle biopsies of 60 consecutive infants were evaluated retrospectively. Twenty three patients had biliary atresia and 37 patients intraheaptic cholestasis(neonatal hepatitis 34, TPN induced jaundice 2 and Dubin-Johnson syndrome 1). All sixty patients underwent Tc-99m DlSIDA hepatobiliary scintigraphy with phenobarbital pretreatment. Of 23 patients with biliary atresia, 22 were correctly interpreted showing 96% sensitivity while of 37 patients with intraheaptic cholestasis, only 12 had intestinal excretion of radionuclide showing 32% specificity. Among the forty needle biopsies, 17 of biliary atresia and 23 of intrahepatic cholestasis, 37 were correctly interpreted as either having biliary atresia or intrahepatic cholestasis. The overall diagnostic accuracy was 93%. Of 3 misdiagnosed cases, the histologic findings of two patients with biliary atresia(aged 43 days and 54 days at the first needle biopsy) were essentially the same as those of neonatal hepatitis. Follow-up biopsies, however, showed findings consistent with biliary atresia. The third one(VLBW premie with history of 8 weeks of TPN) showed mild ductal proliferation and portal fibrosis. This was interpreted as suspicious for biliary atresia. Jaundice resolved gradually. In summary, patients who have intestinal excretion of radionuclide on Tc-99m DlSIDA hepatobiliary scintigraphy, biliary atresia can be ruled out. But the patients who do not have intestinal excretion of radionuclide should have further investigation by needle biopsy. Judicious use of Tc-99m DISIDA hepatobiliary scintigraphy and percutaneous needle biopsy can give a diagnostic accuracy of 95% or more in cases of infantile cholestasis.

• Advances in pediatric surgery
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• v.6 no.1
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• pp.19-26
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• 2000

This paper reports our 9-year experience treating 34 infants with biliary atresia utilizing a new non-invasive diagnostic method, ultrasonographic "triangular cord"(TC) sign. The TC sign is present when there is visualization of a triangular or a band-like echogenicity just cranial to the portal vein. The ultrasonographic TC sign appears to be a simple, non-invasive, time-saving and useful tool in the diagnosis of biliary atresia. Sensitivity is 84 %. Active bile excretion was restored in 90 % of the patients who were treated between 31-60days, 78 % of those between 61-90 days, and 33 % of those being 91days or older. The incidence of postoperative cholangitis was 36 %. Construction of an antireflux valve in the Roux-en-Y loop did not affect the incidence of postoperative cholangitis(p=0.18). Among 34 infants with biliary atresia, 23(68 %) are alive for 2-102 months after operation, and 12 are alive for more than 5 years. Five-year estimate survival by Kaplan-Meier method was 66 %.

• Preventive Nutrition and Food Science
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• v.16 no.2
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• pp.104-109
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• 2011

Recently, we have demonstrated that green tea extract (GTE) decreases the intestinal absorption of benzo[a]pyrene (BAP), which is an extremely lipophilic food contaminant. The present study was conducted to examine if an enteral infusion of GTE would influence the biliary secretion of BAP and lipids in rats. Female rats were fed an AIN-93G diet with or without (control) GTE at 5 g/kg diet for 4 week. Following the 4-week dietary treatment, rats with bile duct cannula were infused continuously for 8 hr at 3.0 mL/hr via a duodenal catheter with a lipid emulsion containing $4.0\;{\mu}mol$ BAP labeled with $^{14}C$ ($^{14}C$-BAP), $20.7\;{\mu}mol$ cholesterol, $452\;{\mu}mol$ triolein, and $3.1\;{\mu}mol$ ${\alpha}$-tocopherol, and $396.0\;{\mu}mol$ Na-taurocholate with or without 76.1 mg GTE powder in PBS buffer (pH, 6.4). Bile was collected hourly via bile cannula for an 8 hr period. Our results showed that bile flow did not differ between groups. However, the biliary secretion of $^{14}C$-BAP was significantly enhanced by GTE infusion, compared with those infused with the lipid emulsion alone. However, GTE did not affect the biliary outputs of cholesterol, fat, phospholipid and ${\alpha}$-tocopherol. These findings indicate that GTE has a profound stimulatory effect on the biliary excretion of BAP in rats, without affecting other biliary lipids. The mechanism(s) by which GTE enhances the biliary secretion of BAP remains to be investigated.

• YAKHAK HOEJI
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• v.38 no.6
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• pp.646-653
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• 1994

The pharmacokinetics of DWP305, a new combined preparation for hepatic disorders was examined in rats. DWP305 was composed of ursodeoxycholic acid(UDCA), Cardus marianus extract(silymarin 74.5%), fursulthiamine and riboflavin tetrabutyrate(RTB). Especially, this study was focused on the possibilities of drug interaction that the administration of DWP305 may affect the oral absorption of each component. After oral administration of DWP305 and each component drug to rats, the biliary excretion of silybin and tauroursodeoxycholic acid(TUDCA), and the urinary excretion of vitamins were measured by HPLC up to 48 hours. The cumulative amount of TUDCA or silybin in bile was not significantly different between DWP305 and UDCA/silymarin administered groups at doses of 25 and 100 mg/kg. In the case of vitamin study, the urinary thiamine excretion of equivalent molar fursulthiamine administered group was significantly higher than that of thiamine administered group. Urinary riboflavin level of equivalent molar RTB administered group was lower than that of riboflavin administered group, but not significant. These results suggest that the combined preparation may not affect the oral absorption of each component in respect of drug interaction. Also, fursulthiamine and RTB were more effective in oral absorption than thiamine and riboflavin, respectively.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.108-108
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• 1995

Pharmacokinetic studies on time-course of blood levels, tissue distribution, and excretion of G009, a potential hepatoprotective agent, were performed in male rats after a single oral dose(20mg/kg) of $\^$14/C-labelled G009. The radioactivity concentrations in plasma during 0～3 hours are low, but subsequently increase to a maximum at 12 hours after dosing. $\^$14/C-G009 was well distributed to all tissue. Tissue concentration profiles of radioactivity vary among tissues on time-course after administration. G009(single oral dosage) was distributed and/or absorbed at gastric intestines and excretional organs for initial time of 0-7 hours, and distributed to most tissue at 12-24 hours. In special, the concentration of radioactivity in tiller at 48 hours were 1% of total radioactivity of $\^$14/C-G009 administered. The expired air, urinary and fecal excretion of radioactivity within 24hours after administration were 61.5%, 1.9% and 21.2% of total radioactivity of $\^$14/C-G009 administered. The biliary excretion of radioactivity in rat increased slightly for 0-6 hours after administration. The biliary excretion of radioactivity within 48hours were 1.97%.

• Advances in pediatric surgery
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• v.17 no.1
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• pp.1-14
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• 2011

Biliary atresia (BA) is an infantile cholestatic disease of progressive obliterative cholangiopathy with varying degrees of damage to both extra and intrahepatic bile ducts due to unknown causes. The diagnostic studies should be done to diagnose or exclude BA without unnecessary delay. Kasai portoenterostomy is the first choice of treatment for bile drainage from microscopic bile ductules present in the portal fibrous mass. The medical management after Kasai portoenterostomy should be done carefully to maintain bile excretion and prevent and treat complications Including cholangitis, hepatic fibrosis, portal hypertension and nutritional problem. The reported five years-survival rates after Kasai portoenterostomy range from 30 to 60 %. About 20 % of all patients undergoing Kasai portoenterostomy during infancy survive into adulthood with their native liver. Even if Kasai portoenterostomy remains as the first line of treatment In BA, liver transplantation serves as a good salvage treatment when portoenterostomy fails or liver function gradually deteriorates after initially successful establishment of bile flow, Overall 5-year survival rate in BA is about 90 % in recent series.

• Korean Journal of Veterinary Research
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• v.36 no.1
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• pp.57-63
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• 1996

The biliary excretion kinetics of the active folate derivatives were examined after an intravenous injection of methotrexate at doses of 0.3 and 10mg/kg to clarify the mechanism of the acute decrease in the plasma folate by the dihydrofolate reductase inhibitors. Even at a higher dose than used in the clinical therapy, methotrexate did not cause any acute depletion of folate denvatives in the excreted bile. Therefore, the decrease in the plasma folate appeared not to be related with the biliary excretion process of folates. A factor responsible for the plasma folate depletion by DHFR inhibitors may be due to the malabsorption of folate derivatives excreted into the small intestine.