• 약학회지
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• 제39권3호
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• pp.223-230
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• 1995

The phannacokinetics and tissue distribution of DWQ-013, a new quinolone, were examined in rats and mice following a single intravenous and oral administration. DWQ-013 in plasma and urine was determined by both HPLC and microbiological assay. The plasma concentration of the drug declined biexponentially. The terminal half life of the drug was 11.11$\pm$0.14 hour after intravenous dosing. The volume of distribution at terminal elimination phase(Vd$_\beta$) and total clearance of the drug were 1.29$\pm$0.15 l/kg and 0.78$\pm$0.09 l/h/kg. The bioavailability of DWQ-013 after oral administration was 56.0% (HPLC) and 77.2%(bioassay), respectively. Twelve-hour urinary recovery of drug was measured by HPLC and bioassay to 0.035$\pm$0009% and 4.71$\pm$066% after oral dosing, to 0.055$\pm$0.014% and 7.65$\pm$1.53% after intravenous dosing, which may indicate the presence of biologically active metabolites. Binding of the drug to plasma proteins ranged from 97%~99% at various concentrations. The drug was highly distributed in order of liver, kidney and lung after 1.5 hours in mice.

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1993년도 제27차 학술대회 초록집
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• pp.67-67
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• 1993

기관 및 후두의 점막표면은 중이나 이관과 마찬가지로 점막섬모 정화작용, 면역글로린, 항세균 효소 등의 다양한 점막 방어기전에 의해 보호되고 있는데 기관 및 후두의 분비선과 분비세포의 형태에 관한 보고는 많으나 분비활성도와 연관된 분비조직의 발생에 대한 연구는 충분치 못하다. 저자들은 백서 기관 및 후두의 분비조직의 발생을 알아보고 향후 기관 및 후두의 발생형태학적 연구의 기초자료로 삼기 위해서 임신 16일부터 생후 21사이의 백서를 이용하여 H & E 염색, AB-PAS 염색과 lysozyme의 면역조직화학적 방법을 통하여 백서 기관 및 후두분비조직의 발달을 연구하였다. 그 결과 백서 기관 및 후두의 분비기능은 출생후 폐의 통기와 함께 활성화되는 것으로 해석되었다.

• 대한한방소아과학회지
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• 제21권2호
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• pp.69-88
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• 2007

Objectives In this study, we investigated the clinical effect of Imoyongsutang and Imoyongsutang plus Maduryong on the viscosity of mucin solution, the instantly type allergy, the delayed type allergy, the carbon clearance, the pulmonary thromboembolism for the lung damaged rats and mice. Methods The gastric mucin and incubation time, pulmonary thromboembolism induced by sodium arachidonic acid, the pulmonary thromboembolism induced by ADP, vascular permeability response, non inhibitory effects, the delayed type hypersensitivity response to picryl chloride, serum $Na^+$ level, $K^+$ and $Cl^-$ level, ${\alpha}-index$ in phagocytic activity were measured. Results 1. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong gave some high significance results on the gastric mucin and incubation time on the viscosity of mucin solution in rats, and both groups had similar result. 2. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed feeble effect on the pulmonary thromboembolism induced by sodium arachidonic acid in mice, and both groups had similar result. 3. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed feeble effect on the pulmonary thromboembolism induced by ADP in mice, and after medication, the value was increased than the before one. 4. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were recognized. significance on vascular permeability response induced by histamine in rats. And the significance of the Imoyongsutang plus Maduryong is rather higher than that of Imoyongsutang. 5. The extract of Imoyongsutang recognized no significance symptoms on vascular permeability response induced by serotonin in rats, but the solid extract of Imoyongsutang plus Maduryong resulted recognized significance. 6. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed non inhibitory effects on the 48 hour homologous PCA in rats provoked by the IgE-like antibody against the egg albumin. 7. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were remarkably revealed inhibitory effect on the delayed type hypersensitivity response to picryl chloride in mice. And the significance of the latter is rather higher than that of the former. 8. The solid extract of Imoyongsutang was revealed inhibitory eects on the delayed type hypersensitivity response to SRBC in mice, but thffe solid extract of Imoyongsutang plus Maduryong recognized significance. 9. The solid extract of Imoyongsutang was recognized significance on the lung TBA value of $O_3$ intoxicated rats, but the solid extract of Imoyongsutang plus Maduryong recognized no significance. 10. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong was recognized significance on serum $Na^+$ level in $O_{3}-intoxicated$ rats. And the significance of the latter is rather higher than that of the former. 11. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed non inhibitory effects on serum $K^+$ and $CL^-$ level $O_{3}-intoxicated$ Rats 12. The solid extracts Imoyongsutang was recognized significance on K-index in phagocytic activity in mice, but the solid extract of Imoymgsutang plus Maduryong recognized no significance. 13. The solid extract Imoyongsutang was recognized on significance on ${\alpha}-index$ in phagocytic activity in mice. but the solid extract of Imoyongsutang plus Maduryong recognized significance. Conclusions According to the above findings, it is suggested that the sold extract of Imoyongsutang and Imoyongsutang plus Maduryong were revealed effects on asthma cough or dyspnea caused by the abnormal rising of lung-allergy and throat discomfort so that they retain effectiveness on the instantly and delayed type allergy, the pulmonary thromboembolism and the lung damages in rats and mice.

• 대한수의학회지
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• 제57권2호
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• pp.105-111
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• 2017

Hyaluronic acid (HA) has been investigated for biomedical and pharmaceutical applications. This study was conducted to determine the distributions of HA nanoparticles (NPs; size 350-400 nm) and larger HA polymers in mice at intervals after application. $^{177}Lutetium$ (Lu)-labeled HA-NPs or HA polymers were intravenously injected (5 mg/kg) into male ICR mice, and radioactivity levels in blood and target organs were measured from 0.25 h to 28 days post-injection. In blood, the radioactivities of HA-NPs and HA polymer peaked at 0.5 h after injection but were remarkably decreased at 2 h; subsequently, they maintained a constant level until 6 days post-injection. HA-NPs and HA polymers were observed in the liver, spleen, lung, kidney, and heart (in ascending order) but were seldom observed in other organs. After 3 days, both the HA-NP and HA polymer levels showed similar steady decreases in lung, kidney, and heart. However, in liver and spleen, the HA-NP levels tended to decrease gradually after 1 day and both were very low after 14 days, whereas the HA polymer level accumulated for 28 days. The results indicate that HA-NPs, with their faster clearance pattern, may act as a better drug delivery system than HA polymers, especially in the liver and spleen.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.179-186
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• 1997

The pharmacokinetics and tissue distribution of DWP20373, a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20373 in plasma, tissue, and urine was performed by both HPLC and microbiological assay. The plasma drug concentration declined biexponentially both rats and beagle dogs. In the rats, the terminal drug elimination half-life (t$_{1}$2$\beta$/) was 64 min (IV) and 57 min (PO) by bioassay, and 76 min (IV) and 77 min (PO) by HPLC. Whereas in beagle dogs, t$_{1}$2$\beta$/ was 196 min (IV) and 350 min (PO). The volume of distribution at steady-state (Vd$_{ss}$ ) was 811 ml/kg (bioassay) and 2061 ml/kg (HPLC) in rats, and 2738 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20373 was 10 ml/min/kg (bioassay) and 7 ml/min/kg (HPLC) in rats, and 11 m1/min/kg (bioassay) in beagle dogs. The extent of bioavailability after oral administration was 49% (bioassay) and 67% (HPLC) in rats, and 84% (bioassay) in beagle dogs. The 24-h urinary recovery, measured by bioassay, was 2.7% after oral dosing and 5.5% after intravenous dosing in rats. Serum protein binding ratio determined at 27g/ml was 78%. This drug was also distributed in tissues in the decreasing order of liver, kidney, spleen, lung, heart, and muscle determined at 30 min after oral administration.on.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.553-558
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• 2017

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7-2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

• Biomolecules & Therapeutics
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• 제8권2호
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• pp.194-198
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• 2000

Taurine, 2-aminoethanesulfonic acid is widely distributed in animal tissues and has a variety of bio-logical activities. A recent worldwide study demonstrated beneficial effects of taurine on aging and age-associated disorders. In general, taurine levels in the brain decease when an animal is subjected to pathologic conditions such as ischemia-anoxia and seizure. But the taurine levles tend to increase in the brain in hypertensive state. In the present study, the blood-brain barrier (BBB) transport of [$^3$H]taurine was compared between spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley rats (SD) using intravenous injection technique in vivo. We also obtained pharmacokinetic parameters of plasma volume maker, [$^{14}$ C] sucrose and [$^3$H]taurine after inject to rats simulatenously. BBB permeability surface area product (PS) value of [$^3$H]taurine in SHR (16$\pm$2.9$\times$10$^{-3}$ ml/min/g) was significantly higher than that in SD (7.4$\pm$0.8$\times$10$^{-3}$ ml/min/g). There is also significant difference for brain uptake of [$^3$H]taurine between SHR (0.195$\pm$0.031%ID/g) and SD (0.058$\pm$0.003% ID/g). This is due to difference of area under the plasma concentration-time curve (AUC) and that of total clearance (Class) between SHR and SD. No significant difference was indicated from other organ uptakes such as lung, heart, liver SHR and SD. But also kidney uptake was much higher in SHR. In conclusion, [$^3$H]taurine in plasma was slowly eliminated in SHR than in SD and uptake of [$^3$H]taurine in SHR is much higher than that of SD. This results suggest increased taurine level in the brain in hypertension state have an any effect on the brain uptake of taurine.

• Biomolecules & Therapeutics
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• 제5권4호
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• pp.419-425
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• 1997

The pharmacokinetics of DWP20364 (1-cyclopropyl -5-amino-6,8-difluoro-7-(2,7-diazabiclo [3,3,0] oct-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone containing C7-bicyc-talc structure, were compared with those of ciprofloxacin (CPFX) after single intravenous (i.v.) and oral (p.o.) administration to rats using microbiological assay (bioassay). After i.v. administration to rats, the plasma concentrations of the two drugs declined biexponentially. The terminal half-lives (t$_{1}$2$\beta$/) of DWP20364 were 110$\pm$ 13.2 min and 117$\pm$3.09 min after i.v. and p.o. administration, respectively, and they were significantly higher than those of CPFX (45.5$\pm$9.52 min and 48.3$\pm$ 12.1 min, respectively). Similar results were also obtained from plasma concentrations and area under the plasma concentration-time curves. The total body clearance of DWP20364, 7.82$\pm$0.37 ml/min/kg was significantly slower than that of CPFX, 27.3 $\pm$ 11.1 m1/ min/kg. Above data suggested that the antimicrobial activity of DWP20364 could be longer than that of CPFX. The urinary recovery after i.v. and p.o. administration of DWP20364 was significantly lower than those of CPFX suggesting that the effect of DWP20364 on urinary tract infection could be lower than that of CPFX. The serum protein binding values of DWP20364 at 2$\mu$g/ml were apparently 91.5~93.1% in rats and human. DWP20364 was distributed by the order of liver, lung, kidney, sf)leon, heart, muscle and brain collected at 30 min after orally administered.

• Tuberculosis and Respiratory Diseases
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• 제43권2호
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• pp.251-256
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• 1996

Kartagener 증후군은 역위, 부비동염 및 기관지 확장증을 보이는 질환으로 일종의 섬모운동장애증후군으로 여겨지고 있다. 저자들은 어렸을 때부터 호흡기 감염이 빈번한 젊은 여성에서 호흡부전과 우심부전을 동반한 Kartagener 증후군 1예를 경험하였기에 이에 문헌고찰과 함께 보고하는 바이다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.317-334
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• 2002

Ginsenosides are metabolized (deglycosylated) by intestinal bacteria to active forms after oral administration. 20(S)-Protopanaxadiol $20-O-{\beta}-D-glucopyranoside$ (M1) and 20(S)-protopanaxatriol (M4) are the main intestinal bacterial metabolites (IBMs) of protopanaxadiol- and protopanaxatriol-type glycosides. M1 was selectively accumulated into the liver soon after its intravenous (i.v.) administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EMl) in the liver. EM1 was isolated from rats in a recovery dose of approximately $24mol\%.$ Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as Ml was, it was accumulated in the liver longer than M1. The in vitro cytotoxicity of M1 was attenuated by fatty acid esterification, implying that esterification is a detoxification reaction. However, esterified M1 (EM1) inhibited the growth of B16 melanoma more than Ml in vivo. The in vivo antitumor activity paralleled with the pharmacokinetic behavior. In the case of M4, orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its spreading to other organs in the body and excretion as bile. The administration of M4 prior to tumor injection abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GMl. Both EM1 and EM4 did not directly affect tumor growth in vitro, whereas EM1 promoted tumor cell lysis by lymphocytes, particularly non-adherent splenocytes, and EM4 stimulated splenic NK cells to become cytotoxic to tumor cells. Thus, the esterification of IBM with fatty acids potentiated the antitumor activity of parental IBM through delay of the clearance and through immunostimulation. These results suggest that the fatty acid conjugates of IBMs may be the real active principles of ginsenosides in the body.