• 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.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.82-86
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• 1997

Pharmacokinetics of a new capsaicin analog, DA-5018 were evaluated after a subcutaneous injection or topical application of $[^{14}C]$--labelled or unlabelled DA-5018 to rats and rabbits. After subcutaneous injection of $_{14}$c-labelled or unlabelled DA-5018, 0.5 mg/kg (equivalent to DA-5018) to rats, the plasma total activity peaked at 2 hr with the terminal half life of 5.34 hr, however, unlabelled-DA-5018 peaked at 1 hr with the terminal half life of 1.26 hr. Moreover, the AUC (0.726 versus 0.2337g hr/ml) and MRT (7.82 versus 3.55 hr) increased significantly based on total radioactivity compared with intact DA-5018. Above data indicated that DA-5018 is extensively metabolized in rats and the terminal half- life of the metabolite(5) had a longer half-life than that of DA-5018. The cumulative percentages of biliary excretion of dose after subcutaneous injection of $[^{14}C]$DA-5018 was 40.2%, however, the value was only 2.14% when unlabelled DA-5018 was injected. After topical application of 0.1% or 0.3% $_{14}$C-labelled or unlabelled DA-5018 cream, 500 mg/kg to rats, the plasma and tissue concentrations except applied skin were under the detection limit. After consecutive 7 days topical application of unlabelled DA-5018, 0.1% and 0.3% cream to rats, the plasma concentrations were also under the detection limit. But the urinary excretion of DA-5018 was significantly increased by repeated topical administration. After topical application of unlabelled DA-5018, 0.1% and 0.3% cream to rabbits, the plasma and urine concentrations were under the detection limit. Above data indicated that the skin permeation of DA-5018 was lower and the metabolism of DA-5018 was higher in rabbits than that in rats.

• 약학회지
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• 제37권4호
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• pp.383-388
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• 1993

Pharmacokinetics of aucubin, an irdoid glucoside, was compared in rats of experimental hepatic failure(EHF). EHF was induced by CCI$_{4}$ or D-galactosamine pretreatment. This work was designed to find out any differences in the pharmacokinetics of aucubin that may explain the different protective effect of aucubin on CCI$_{4}$- and galactosamine-induced EHF : aucubin reportedly protected CCI$_{4}$-inducing hepatotoxicity effectively, but did not for galactosamine-hepatotoxicity. EHF was induced by intraperitoneal injection Of CCI$_{4}$(0.9ml/kg) or galactosamine(250 mg/kg) to Wistar rats 24 hr before the pharmacokinetic study. The rats were fasted during the 24 hr. Aucubin was iv injected at a dose of 15 mg/kg and the plasma aucubin was assayed by HPLC. There were no significant differences in the pathophysiologies(body weight, liver weight, GTP, hematocrit, blood cell distrbution and plasma protein binding of aucubin) between the two EHF models except GOP which was significantly (p<0.05) higher in CCI$_{4}$-than in galactosamine-EHF. On the other hand, pharmacokinetics of aucubin such as total cleatance(CL$_{t}$), distribution volume at steady-state(Vd$_{ss}$), and mean residence time(MRT) differed significantly(p<0.05) between the models : for example, CL$_{t}$ was increased two fold by CCI$_{4}$, but not by galaclosamine ; Vd$_{ss}$, in galactosamine-EHF was higher than that in CCI$_{4}$-EHF ; MRT was decreased by CCI$_{4}$, but increased conversely by galactosamine. The increase of CL$_{t}$(and decrease of MRT) in rats of CCI$_{4}$-EHF was contrary to the general expectation for the hepatic failure : most of the hepatic failures have been known to decrease CL$_{t}$ of the administered drugs. Whether the difference in the pharmacokinetics is responsible for the different protective effect of aucubin against the two EHF models is of interest. However, much more studies on biliary excretion, urinary excretion, and hepatic uptake in cellular level should be preceded before any conclusions are made on the role of different pharmacokinetics on the different pharmacology of aucubin.

• 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.

• Archives of Pharmacal Research
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• 제9권2호
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• pp.111-114
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• 1986

Bretylium tosylate is a quaternary ammonium compound used for the treatment of ventricular fibrilation in humans. It is advantageous to other cationic compound in the study of biliary excretion in that negligible amount is bound to plasma protein and metabolite is not likely is to be formed. Some researchers reported that the formation of ion-pair complex caused to increase the lipothilicity of cationic compound. The partition of bretylium between water and organic phase was increased with the addition of sodium taurodeoxycholate. Also sensitive gas chromatographical assay procedure using flame ionization detector was studied. This procedure can detect as low as 0.1 mg/ml using 0.1 ml biological sample, but contamination by previous injection is the major problem of this method.

• Archives of Pharmacal Research
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• 제13권3호
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• pp.227-232
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• 1990

A Physiologically based pharmacokinetic model was used to describe the distribition and elimination of cefriazone in the rat. To validate the practical application of the model, the effect of cffeine on the model was also examined. The model consisted of eleven compartments representing the major sites for ceftriaxone distribution including carcass which served as a residual compartment. Elimination was represented by renal and hepatic (metabolic biliary )excretion with GI secretion and re-absorption. The drug concentrations in most of the tissues were simulated using flow limited equations while brain levels were simulated using membrane limited passive diffusion distribution. The experimental data were obtained by averaging the concentration of drug in the plasma and tissues of five rats after i. v. injection of cefriazone 100 mg/kg without and with caffeine 20 mg/kg. The data for the amount of ceftriazone excreted in urine and gut contents were used to apportion total body clearance. HPLC with UV detection was used for the assay with 0.1-0.2 $\mu$g/ml sensitivity. The great majority of drug concentrations with and without caffeine show reasonably good agreements to the simulation results within 20%. The effect of caffeine on renal and hepatic clearances was apparent with 18.8% and 18.6% increase in the model values, respectively.

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2003년도 Challenges and Achievements in Environmental Health
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• pp.157-157
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• 2003

To evaluate an effect of pathological liver damage on the cyclohexane metabolism, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1$\mell$/100g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function and histological findings, the animals pretreated with $CCl_4$ 10 times were identified as acutely liver damaged ones and the animals pretreated with $CCl_4$ 17 times were identified as severly liver damaged ones, with fibrosis, biliary abnormality and mild injury both in the kidneys and the lungs. To these liver damaged animals, cyclohexane (a single dose of 1.56g/kg body weight, i.p.) was administrated at 48 hours after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hours after injection of cyclohexane. The cyclohexane metabolites; cyclohexanol (CH-ol), cyclohexane-1, 2-diol (CH-1, 2-diol), cyclohexane-l, 4-diol (CH-1, 4-diol), and their glucuronyl conjugates and cyclohexanone (CH-one) were detected in the urine of cyclohexane treated rats. After cyclohexane treatment, the serum levels of CH-ol and CH-one were remarkably increased at 4 hours and then decreased at 8 hours in normal group. Whereas in liver damaged rats, these cyclohexane metabolites were higher at 8 hours than at 4 hours. The excretion rate of cyclohexane metabolites from serum into urine was more decreased in liver damaged animals than normal group, with the levels of excretion rate being lower in $CCl_4$ 17 times injected animals than 10 times injected ones. However, it was interesting that the urinary concentration of cyclohexane metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. And liver damaged rats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to cyclohexanol analogues compared with normal group. Futhermore, CH-1, 2 and 1, 4-diol were all conjugated with glucuronic acid in $CCl_4$ 17 times injected animals. In conclusion, the metabolic rate of cyclohexane was unexpectably accelerated and it may be caused by physiological adaptation of adjacent intact hepatocyte in damaged liver.

• Biomolecules & Therapeutics
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• 제11권3호
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• pp.163-168
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• 2003

Pharmacokinetics of eupatilin (an active components of $Stillen^{\circledR}$, a new antigastritic agent) were investigated after both intravenous and oral administration at a dose of 30mg/kg to rats. After intravenous administration, the plasma concentrations of unchanged eupatilin declined rapidly with a mean terminal half-life of 0.101 h. Eupatilin was eliminated fast in rats; the total body clearance was 121 mL/min/kg. Eupatilin was mainly metabolized in rats; the percentage of intravenous dose of eupatilin excreted in 24 h urine and feces as unchanged eupatilin was only 2.5 and 0.919％, respectively. Eupatilin was mainly metabolized to form its glucuronide conjugate; after intravenous administration, 15.9 and 51.7％ of intravenous dose was excreted in 24 h urine and feces, respectively, as eupatilin plus its glucuronide. After oral administration, the absolute bioavailability was only 3.86％ based on $AUC_{0-24h}$ of eupatilin plus its glucuronide. Approximately 68.5％ of oral dose was not absorbed from the entire gastrointestinal tract. Therefore, it could be concluded that the superior effect of eupatilin in experimental animal models of gastric ulcer and inflammatory bowel disease after oral administration could be due to the local action of eupatilin. Further pharmacokinetic studies to elucidate the local action of eupatilin are required.

• 대한수의학회지
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• 제35권4호
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• pp.659-670
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• 1995

Cyclosporin A extracted from fungus Trichoderma polysporum Rifai and Cyclindrocarpon lucidum Booth serves as an important immunosuppressive drug in transplantation surgery. Systemic treatment with cyclosporin A induces an impairment of the biliary excretion of the bile salts and cholestasis. This study was designed to observe the Ultrastural changes of the hepatocytes and the bile canaliculi in cyclosporin A-induced intrahepatic cholestasis in rats. Cyclosporin A was injected into male Wistar rats intraperitoneally 50mg per kg body weight and rats were necropsied at 1, 3, 6, 9, 12, 24 hours. The liver tissues were observed with transmission and scanning electron microscopes and the results were as follows. Transmission electron microscopy: After cyclosporin A injection, SER and lysosomes were increased in the hepatocytes until 9 hours. At 12 hours after injection of cyclosporin A, RER with dilated cistern were increased, and SER, lysosomes in the cytoplasm were decreased. From 1 hour to 24 hours after injection of cyclosporin A, there were dilation of bile canalliculi and decreased or lost microvilli. At 24 hours the dilation of bile canaliculi were decreased. Scanning electron microsocopy: After cyclosporin A injection, the bile canaliculi were dilated and the microvilli were shortened, decreased or lost according to the sites. At 24 hours, the microvilli packing the bile canaliculi were observed. These observations suggest that cyclosporin A-induced cholestasis is associated with the dilation of bile canaliculi, increased microfilaments of the pericanalicular region and decreased or lost microvilli.

• 농약과학회지
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• 제10권4호
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• pp.289-295
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• 2006

살충제 imidacloprid(1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine)의 붕어(Carassius auratus L.) 체내 행적과 장기에 미치는 영향을 구명하기 위하여 imidacloprid를 환경추정농도인 0.064 mg $kg^{-1}$로 처리한 시험수에 붕어를 4일간 경시적으로 노출시켰다. 수중의 imidacloprid는 붕어체내에 흡수되어 노출 2일차에 최대 흡수량을 나타내었으며, 다른 장기에 비해 쓸개에서 농도가 가장 높았다. 붕어 사육수에서 미확인 주대사산물과 imidacloprid urea가 대사산물로 검출되었다. 또한 붕어체내에 흡수된 imidacloprid의 주요 배설경로는 담도이었으며, 장기에 대한 조직학적 이상증상은 발견되지 않았다.