• Biomolecules & Therapeutics
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• 제1권1호
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• pp.50-57
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• 1993

This study characterized the effect of liver injury produced by hepatotoxicants on the biliary and urinary excretion of acetaminophen(AA) metabolites. Liver damage was produced in male S.-D. rats, 24 hr after dosing with carbon tetrachloride(4CCl_4,$ 0.75 mι/kg, ip) or thioacetamide(TA, 200 mg/kg, ip), or 16 hr after administration of cadmium chloride(4CdCl_2,$ 3.9 mg/kg, iv). Liver damage without renal injury was confirmed by measuring serum enzymes, creatinine and BUN levels as well as by histopathological examination. AA and its metabolites were measured for 3 hr by HPLC in rats injected iv with 1 mmo1/kg of AA. The excreted amounts of AA-glucuronide into bile were reduced to 60~70% of control rats by hepatotoxicants, but did not change urinary excretion of AA-glucuronide and AA-sulfate. Treatments with $CCl_4,\; CdCl_2$ and TA decreased the total (biliary plus urinary) excretion of thioethers of AA(30~50% of control), suggesting that these toxicants decrease cytochrome P-450-mediated toxification of AA. However, treatments of $CdCl_2$and TA markedly enhanced the excretion of AA-mercapturate into urine. Thus, 4CdCl_2$ and TA not only influence the formation of AA-glutathione, but may also alter the excretory routes (i.e. bile and urine) for the elimination of AA-metabolite.

• 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.

• 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.

• 약학회지
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• 제27권2호
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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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%.

• Journal of Microbiology and Biotechnology
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• 제19권12호
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• pp.1569-1572
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• 2009

The pharmacokinetics of decursin and decursinol angelate (D/DA) were investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The levels of D/DA and metabolized decursinol in the blood following oral and intravenous administrations declined according to first-order kinetics, with $T_{1/2}$ values of 56.67, 58.01, and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretions of D/DA in bile duct-cannulated rats was $36.10{\pm}2.9%$, $25.35{\pm}3.8%$, and $34.20{\pm}3.2%$, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.