흰쥐에서 UDCA와 Silymarin을 함유한 간장질환 치료용 의약조성물(DWP305)의 담즙 및 요중 배설

남권호(Kweon Ho Nam),김동오(Dong O Kim),조재열(Jae Youl Cho),염제호(Je Ho Yeom),김영만(Young Man Kim),유은숙(Eun Sook Yoo),유영효(Young Hyo Yu),박명환(Myung Hwan Park) 대한약학회 1994 약학회지 Vol.38 No.6

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(TLJDCA), and the urinary excretion of vitamins were measured by HPLC up to 48 hours. The cumulative amount of TLTDCA or silybin in bile was not significantly different between DWP305 and UDCA/silymarin administered groups at doses of 25 and 100mg/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 in teraction. Also, fursulthiamine and RTB were more effective in oral absorption than thiamine and riboflavin, respectively.

흰쥐에 재조합 인간 상피세포 성장인자(DWP401)를 연용피하투여했을 때 약물체내동태

남권호(Kweon Ho Nam),조재열(Jae Youl Cho),정주영(Joo Young Chung),장우익(Woo Ik Chang),강진석(Jin Seok Kang),유은숙(Eun Sook Yoo),박승국(Seung Kook Park),유영효(Young Hyo Yu),박명환(Myung Hwan Park),심창구(Chang Koo Shim) 대한약학회 1996 약학회지 Vol.40 No.5

The organ distribution and pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), were compared after single and repeated subcutaneous administration (50mcg/kg, 10mcCi/kg of 125I-DWP401, twice a day for 7 consecutive days) to rats. The pharmacokinetic parameters such as AUC and terminal half-life were similar between two different administration. During repeated administration, the plasma concentration of DWP401 seemed to be constant when the plasma was collected at 15 min after each dosing. The TCA-precipitated radioactivities in thyroid, liver, kidney, and stomach were higher than those of other organs studied after both single and repeated administration. The TCA-precipitated radioactivities after repeated administration in several organs, such as thyroid, stomach, prostate, adrenal, eye ball, and testis were higher than those after single administration. But, according to the observations using gel filtration chromatography and antibody binding assay, the radioactivities in thyroid and stomach were not primarily due to the intact DWP401 or its metabolites but due to the 125I-thyroxine binding protein. In conclusion, it can be suggested that DWP401 is metabolized to each amino acid or small polypeptides, and there was no significant changes in pharmacokinetics or any indications for accumulation of DWP401 in rat plasma and organs after repeated treatment.

고주파 초음파 스페클 분석기법을 이용한 혈액의 응고과정 측정

남권호(Kweon-Ho Nam),염은섭(Eunseop Yeom),하호진(Hojin Ha),이상준(Sang-Joon Lee) 대한기계학회 2011 대한기계학회 춘추학술대회 Vol.2011 No.4

유제화에 의한 경구용 항암제인 테가푸르의 장관 임파수송

이용복,남권호,장우익,오인준,고익배,Lee, Yong-Bok,Nam, Kweon-Ho,Chang, Woo-Ik,Oh, In-Joon,Koh, Ik-Bae 한국약제학회 1995 Journal of Pharmaceutical Investigation Vol.25 No.1

W/O and O/W emulsions of tegafur (50 mg/5 ml/kg) were orally administered to rats to compare with their mesenteric lymphatic delivery effects. And also in order to demonstrate the lymph targeting associated to the oral route, it was deemed necessary to investigate the fate of solution after oral administration as a control. Lymph and plasma samples were periodically taken from each subject of mesenteric lymphatic duct cannulated rats. Then, lymph and plasma levels of tegafur and its active metabolite, 5-FU, were simultaneously observed. Also pharmacokinetic parameters were compared with each others. On the other hand, most previous studies of lymphatic transport have not addressed the question of whether an increase in mesenteric or thoracic lymph transport by the manipulation of a suspected variable was due to a selective delivery to the intestinal lymphatics or an overall increase availability. Therefore, based on a physiologically based pharmacokinetic model which represents the characteristics of lymphatic systems, we are also going to determine the contributions of mesenteric lymph transport versus thoracic lymph transport of tegafur reported in reference(13). In comparison with tegafur solution, AUC and mean residence time of plasma tegafur were significantly increased in W/O emulsion but significantly decreased in O/W emulsion. Lymph flow rates were similar in both solution and W/O emulsion but half in O/W emulsion. AUC of tegafur in mesenteric lymph and in plasma for W/O emulsion were 3.7 times and 2.9 times more than those for O/W emulsion, respectively. And AUC of 5-FU in thoracic lymph for W/O emulsion was 3.7 times more than that for O/W emulsion. These results suggested that lymphatic delivery or tegafur by W/O emulsion was more effective than that by on emulsion due to its differences or formation ability of chylomicrons.

위장질환 치료용 의약조성물 (DWP 302) 의 일반약리작용

김영만,남권호,유영효,임승욱,염제호,장병수,김동오,박명환 한국응용약물학회 1993 Biomolecules & Therapeutics(구 응용약물학회지) Vol.1 No.2

The general and some pharmacological actions of DWP 302 were investigated in animals and the following results were obtained. In central nervous system, DWP 302 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in the mice and body temperature in the rat. DWP 302 showed no depressive action on the convulsion induced by strychnine and electronic shock. From these results, DWP 302 was considered to have no or little pharmacological effect on the central nervous system. Furthermore, DWP 302 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 302 showed neither contractive nor relaxing effects against the acetylcholine (10^(-6) g/ml), histamine (10^(-6) g/ml) and BaCl₂ (10⁴g/ml) at a concentration of 1.9X 10⁴g/ml in bath. But it caused a slight increase in basal tone at a concentration of 6.3 X 10^(-4) g/ml and this effect was inhibited by atropine 10^7 g/ml. In the isolated trachea and vas deference, DWP 302 showed no effect on the contractions produced by histamine and norepinephrine, respectively. And DWP 302 showed no effect on the contractions producd by acetylcholine and oxytocin in the isolated nonpregnant rat uterus. DWP 302 had no effect on bile excretion, urine volume, pH and gastrointestinal motility. But, DWP 302 showed a significant inhibitory effect on gastric secretion in the rat.

유제화에 의한 경구용 항암제인 테가푸르의 장관 임파수송

이용복,남권호,장우익,오인준,고익배 전남대학교 약품개발연구소 1996 약품개발연구지 Vol.4 No.1

W/O and O/W emulsions of tegafur (50 ㎎/5 ㎖/㎏) were orally administered to rats to compare with their mesenteric lymphatic delivery effects. And also in order to demonstrate the lymph targeting associated to the oral route, it was deemed necessary to investigate the fate of solution after oral administration as a control. Lymph and plasma samples were periodically taken from each subject of mesenteric lymphatic dud cannulated rats. Then, lymph and plasma levels of tegafur and its alive metabolite. 5-FU, were simultaneously observed. Also pharmacokinetic parameters were compared with each others. On the other hand, most previous studies of lymphatic transport have not addressed the question of whether an increase in mesenteric or thoracic lymph transport by the manipulation of a suspected variable was due to a selective delivery to the intestinal lymphatics or an overall increase availability. Therefore, based on a physiologically based pharmacokinetic model which represents the characteristics of lymphatic systems, we are also going to determine the contributions of mesenteric lymph transport versus thoracic lymph transport of tegafur reported in reference(13). In comparison with tegafur solution, AUC and mean residence time of plasma tegafur were significantly increased in W/O emulsion but significantly decreased in O/W emulsion. Lymph flow rates were similar in both solution and W/O emulsion but half in O/W emulsion. AUC of tegafur in mesenteric lymph and in plasma for W/O emulsion were 3.7 times and 2.9 times more than those for O/W emulsion. respectively. And AUC of 5-FU in thoracic lymph for W/O emulsion was 3.7 times more than that for O/W emulsion. These results suggested that lymphatic delivery of tegafur by W/O emulsion was more effective than that by O/W emulsion due to its differences of formation ability of chylomicrons.

사람 혈장 중 엘도스테인 분석 및 생체이용률 시험

윤복희,이영복,남권호,강지훈,강희경,유은숙 제주대학교 생명과학연구소 2002 제주생명과학연구 Vol.5 No.6

A developed assay method to evaluate the pharmacokinetics of erdosteine in human plasma was investigated by reverse-phase HPLC-UV. We found the analytic condition that separate erdostein from internal standard(citiolone) in human plasma sample at the wavelength of 220 nm. Proteins of the plasma samples were removed enough by using 2M perchloric acid. Mobile phase is consisted of bufferi(pH2.0) : CH_3CN(80:20), and retention time of erdosteine is 5.5 min at a flow rate of 1 ml/min. The fundamental parameters such as linearity, accuracy, precision for this bloanalytical method validation were suitable to pharmacokinetic study and bioequvalence test. Eight volunteers in fasting were administered single dose of 900 mg of erdosteine(3 capsules of 300 mg each) orally together with 240 ml water for pharmacokinetic studies. The maximum concentration(3.80㎍/ml) of erdosteine was attained at 0.94 hour after dosing. T_(1/2) and AUC(0 - 6 hour) were 2.33 hr and 6.91 ㎍ hr/ml respectively. According to our study, the accurate analysis for erdosteine achieved and the proposed guidance can be applied to pharmacokinetic study and bioequvalence test in human.

C7-이환체 구조를 갖는 새로운 플루오로퀴놀론계 항생물질의 흰쥐 체내동태와 조직분포

조재열,한승희,김병오,남권호,손호정,이재욱,유영효,박명환 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.4

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.

Polyoxyl 40 Hydrogenated Castor Oil 이 실리마린과 우루소데옥시콜린산 복합제제중 실리마린의 용해성 및 생체이용률에 미치는 영향

장우익(Woo Ik Chang),남권호(Kweon Ho Nam),조재열(Jae Youl Cho),이재휘(Jae Hwi Lee),유영효(Young Hyo Yu),박명환(Myung Hwan Park),김재환(Jae Hwan Kim) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3

The effect of nonionic surfactant(polyoxyl 40 hydrogenated castor oil, PHCO), a common solubilizer, on the solubility of silymarin in the combined preparation containing ursodeoxycholic acid(UDCA) and silymarin was investigated in vitro using HPLC. The solubility of silybin, a major component of silymarin, was enhanced by increasing the amount of PHCO. The effect of PHCO on bioavailability was also evaluated in rats. The bioavailability was calculated by silybin content in bile juice that was excreted for 24 hr after oral administration. It was found that the bioavailability of silymarin containing PHCO was significantly increased compared to that of control. These results suggest that PHCO may improve the solubility and bioavailabilty of silymarin when it is combined with UDCA and silymarin.

신규 퀴놀론계 항생물질 DWQ-013의 흰쥐 및 생쥐에서의 체내동태

조재열(Jae Youl Cho),남권호(Kweon Ho Nam),김동오(Dong O Kim),이종완(Jong Wan Lee),박남준(Nam Joon park),강영숙(Young Sook Kang),유영효(Young Hyo Yu),이재욱(Jae wook Lee) 대한약학회 1995 약학회지 Vol.39 No.3

The pharmacokinetics 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 biexpohentially. The terminal half life of the drug was 1.11 +/- 0.14 hour after intravenous dosing. The volume of distribution at terminal elimination phase(Vdbeta) and total clearance of the drug were 1.29 +/- 0.15l/kg and 0.78 +/- 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 +/- 0.009% and 4.71 +/- 0.66% after oral dosing, to 0.055 +/- 0.014% and 7.65 +/- 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.