• Journal of Pharmaceutical Investigation
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• 제21권4호
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• pp.201-213
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• 1991

There are many drugs reproted to show unusual pharmacokinetic behavior by producing a significant secondary peak in the plasma concentration-time curve after oral administration. The drugs are ranitidine, cimetidine, acetaminophen, aspirin, furosemide, bumetanide, piretanide, veralipride, sobrerol, penicillamine and doxycycline etc. Enterohepatic circulation-, two absorption site-, biphasic gastric emptying-, tissue deposition- and multi-fraction absorption theories have been suggested for the mechanisms of this phenomenon. Here, the theories were reviewed and critisized for their validity as a possible mechanism of the multiple peak phenomenon.

• 한국식품위생안전성학회지
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• 제5권1호
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• pp.7-12
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• 1990

Radiolabeled Brazilin(^3H-Brazilin)을 웅성 Wistar Rats에 투여하여 plasma concentration-time profile, urine 및 bile로의 배설, 조직분포 및 plasma protein에 대한 결합률을 살펴보았다. 1. Pharmacokinetic parameters는 다음과 같았다. $t_{1/2}$은 13.7 hr, AUC는 $\53.38\;\mu\textrm{g}{\cdot}hr/ml$, AUMC는 $1013.4\;\mu\textrm{g}{\cdot}hr^2/ml$ MRT는 18.95hr, Vss 17.778l/kg 그리고 CL은 936.77ml/hr.kg였다. 2. Plasma concentration-time profile에서 enterohepaic circulation을 시사하여 2nd peak가 발견되었고. 담즙배설 실험으로 확증할 수가 있었다. 결구투여 후 담즙 배설은 투여량의 64.4%가 10시간에 걸쳐 배설되었고, 3시간째 그 배설속도는 maximum을 이뤘다. 3. Vss는 17.8 l/kg으로 큰 값을 나타냈고, 따라서 뇌를 제외한 대부분의 조직에 Brazilin은 분포하였고 특히 liver와 kidney, epididymus 그리고 testis에 고농도 분포함을 알 수 있었다. 4. 경구투여량의 44.1%가 , 정맥주사 후 투여량의 62.9%가 urine을 통해 배설되었다. Urine을 통해 배설되는 양의 대부분(80%)은 24시간 내에 배설되었다. 5. Plasma protein에 대한 결합율을 한외여과법으로 측정한 결과 $40{\pm}4%$가 결합하는 것으로 나타났다.

• The Korean Journal of Physiology and Pharmacology
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• 제16권1호
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• pp.25-30
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• 2012

Under some pathological conditions as bile flow obstruction or liver diseases with the enterohepatic circulation being disrupted, regurgitation of bile acids into the systemic circulation occurs and the plasma level of bile acids increases. Bile acids in circulation may affect the nervous system. We examined this possibility by studying the effects of bile acids on gating of neuronal (N)-type $Ca^{2+}$ channel that is essential for neurotransmitter release at synapses of the peripheral and central nervous system. N-type $Ca^{2+}$ channel currents were recorded from bullfrog sympathetic neuron under a cell-attached mode using 100 mM $Ba^{2+}$ as a charge carrier. Cholic acid (CA, $10^{-6}M$) that is relatively hydrophilic thus less cytotoxic was included in the pipette solution. CA suppressed the open probability of N-type $Ca^{2+}$ channel, which appeared to be due to an increase in (no activity) sweeps. For example, the proportion of sweep in the presence of CA was ~40% at +40 mV as compared with ~8% in the control recorded without CA. Other single channel properties including slope conductance, single channel current amplitude, open and shut times were not significantly affected by CA being present. The results suggest that CA could modulate N-type $Ca^{2+}$ channel gating at a concentration as low as $10^{-6}M$. Bile acids have been shown to activate nonselective cation conductance and depolarize the cell membrane. Under pathological conditions with increased circulating bile acids, CA suppression of N-type $Ca^{2+}$ channel function may be beneficial against overexcitation of the synapses.

• 한국임상약학회지
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• 제21권2호
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• pp.49-56
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• 2011

The family of bile acids belongs to a group of molecular species of acidic steroids with very peculiar biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways and secreted into small intestine for the participation in the digestion and absorption of fat. The bile acids are mostly confined to the territories of the so-called enterohepatic circulation, which includes the liver, the biliary tree, the intestine and the portal blood with which bile acids are returned to the liver. In patients with bile acid malabsorption, the amount of primary bile acids in the colon is increased compared to healthy controls. Although the increase in the secondary bile acids including deoxycholic acid, is reported to have the potency to affect tumorigenesis in gastrointestinal tracts, there is no firm evidence that clinically relevant concentrations of the bile acids induce cancer. The list of their physiological roles, as well as that of the pathological processes is long and still not complete. There is no doubt that many new concepts, pharmaceutical tools and pharmacological uses of bile acids and their derivatives will emerge in the near future.

• 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.

• Asian-Australasian Journal of Animal Sciences
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• 제17권12호
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• pp.1741-1745
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• 2004

Administration of milk and fermented milks produced from indigenous dadih lactic acid bacteria on serum lipids and bile acids, fecal bile acids and microflora was estimated in hypercholesterolemic rats. Anaerobic lactic acid bacteria decreased and coliforms increased in the feces of the control group; however, the number of fecal lactic acid bacteria remained unchanged when rats were administered milk and fermented milks. Only fermented milk made from Lc. lactis subsp. lactis IS-10285 significantly reduced serum total cholesterol, LDL cholesterol and total bile acids. Milk and fermented milks did not influence the HDL cholesterol. Triglyceride and phospholipid levels were significantly lower in the rats fed fermented milk of Lc. lactis subsp. lactis IS-10285 than rats fed milk and fermented milk of Lc. lactis subsp. lactis IS-29862, but not significantly different from the control group. Hypocholesterolemic effect of Lc. lactis subsp. lactis IS-10285 was attributed to its ability to suppress the reabsorption of bile acids into the enterohepatic circulation and to enhance the excretion of bile acids in feces of hypercholesterolemic rats.

• Journal of Dairy Science and Biotechnology
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• 제22권1호
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• pp.13-25
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• 2004

담즙산은 cholesterol의 대사산물로 체내에서 cholesterol을 제거하는 주경로로서, 체내 cholesterol 대사를 조절하는 중요한 수단이다. 최근에 복합담즙산 분해활력이 높은 L. acidophilus에 의한 혈중 cholesterol 저하효과에 관한 많은 연구들이 보고되고 있으며, 이것은 복합담즙산의 분해로 생성되는 유리 담즙산의 분 배출 증가와 장내 cholesterol 흡수에 필요한 복합 micelle 형성의 방해에 의한 것으로 알려져 있다. 즉, 유리 담즙산은 장내에서 복합담즙산보다 용해성이 낮아서 흡수되지 않고 분으로 배출되기 쉬워, 간에서는 분으로 배출된 양만큼의 부족한 복합담즙산을 보충하기 위해 cholesterol을 이용하여 새로운 복합담즙산을 생성하기 때문에 결국은 체내의 혈중 cholesterol 수준을 감소시키는 것으로 생각된다. 또한 담즙으로 분비되는 복합담즙산은 소장내에서 cholesterol의 용해 흡수에 도움을 주지만 유리 담즙산은 cholesterol 용해성이 낮기 때문에, 장내 cholesterol 흡수에 영향을 미치는 것으로 생각된다.

• 약학회지
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• 제41권3호
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• pp.335-344
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• 1997

The absorption, distribution and excretion of $^{14}C$ labeled YH1885 {5,6-Dimethyl-2(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine hydroc hloride), a new proton pumpinhibitor, were investigated in rats after a single administration of $^{14}C$-YH1885. 1. After intravenous administration of 5mg/kg, the blood level of radioactivity declined in a biphasic fashion with the mean terminal elimination half-life of 12.4hr. 2. After oral administration of 20mg/kg, the maximum blood level of radioactirity was reached at 4.0hr in female rats. The blood level of radioactivity-time profiles in male and female rats were similar, and the absorptionof $^{14}C$-YH1885 was not affected by food. 3. Appproximately 89% and 1% of radioactivity of the total dose were excreted in feces and urine, respectively. 4. Biliary excretion of radioactivity was 47.9% of the dose. Enterohepatic circulation of radioactivity was 49.6%. 5. Radioactivity was excreted maily into feces via bile. 6. The concentration of radioactivity in most tissues reached the peak level at 4.0hr after dosing, and then declined. Autoradiograms of male rats showed that the radioactivity levlels in the fat, harder's gland, liver and G-Itract were higher than those in the other tissues and the elimination of radioactivity from fat and liver was slow. 7. Autoradiograms of a pregnant rat showed that radioactivity was transferred to mammary gland, placenta and fetus. The radioactivity level in the mammary gland was higher than that in the blood.