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플루옥세틴 캅셀제의 지원자에 대한 생체이용율 및 대사율 비교
강원구(Won Ku Kang),박용순(Yong Soon Park),조규행(Gyu Haeng Cho),최준식(Jun Sik Choi),권광일(Kwang Il Kwon) 대한약학회 1998 약학회지 Vol.42 No.5
Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake. This study was carried out to compare the bioavailability of Myung-in fluoxetine (20mg/cap.) with that of Prozac(R). The bioavailability was conducted on 24 healthy volunteers who received a single dose (80mg) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After closing, serial blood samples were collected for a period of 48 hours, Plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters (AUC0-48 hr, Cmax, Tmax , AUCinf., MRT. T1/2, Vd and Cl) were, calculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program, `WinNonlin` was used for compartmental analysis. A two-compartment model with first-order input, first-order output and no lag time was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of l/y2. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac(R) at all observed time from 7.9% to 16.9% (P<0.05 at 6.7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac(R). There were no statistical significant differences between the two drugs in all pharmacokinetic parameters including AUC0-48 hr of norfluoxetine.
이혜원 ( Hae Won Lee ),윤영란 ( Mi Sun Lim ),임미선 ( Sook Jin Seong ),성숙진 ( Joo Mi Lee ),이주미 ( Sung Min Park ),박성민 ( Keum Han Noh ),노금한 ( Sung Ho Park ),박성호 ( Eun Jung Kim ),김은정 ( Won Ku Kang ),강원구 ( Young Ra 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0
Modem biologics are biotechnology-derived therapeutics, ineluding recombinant therapeutie proteins like monoclonal antibodies, cytokines and tissue growth factors. Although the pharmacokinetics of therapeutic biologic should be evalu-ated based on the same general principles as small molecules, careful considerations should be given to bioanalyties and phannacokinetics when designing pharmaeokinetic studies of biologics during their drug development, due to their dif-feren physicochemical properties compared with small molecules. The aim of this study was to develop draft guid-ance on pharmacokinetic studies of therapeutic biologics in clinical studies. All the elements outlined in the current Food and Drug. Administration (FDA), European Medicinal Agency (EMEA), and International Conference on Hannom-isation (ICH) guidelines and regulations, and the related literatures previously published were searched and evaluated. In this drall guidance, the specitic problems to the pharmacokinetics of therapeutic biologics that need special consideration sideration during drug development process were addressed, and differences in pharmacokinetic characteristics between biologics and small molecules affecting the content of the development programme were presented.
당뇨병 및 골다공증 치료제의 효율적인 신약개발을 위한 생체표지자 및 대리 결과 변수의 역할 및 활용
성수현,윤휘열,백인환,강원구,장정윤,서경원,권광일,Seong, Soo-Hyeon,Yun, Hwi-Yeol,Baek, In-Hwan,Kang, Won-Ku,Chang, Jung-Yun,Seo, Kyung-Won,Kwon, Kwang-Il 대한약학회 2008 약학회지 Vol.52 No.5
Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.
원보 : LC/MS/MS를 이용한 비글견의 혈장 중 Doxifluridine 및 5-Fluorouracil의 동시 분석법 Validation
김기환 ( Ghee Hwan Kim ),김원 ( Won Kim ),김진성 ( Jin Sung Kim ),김경일 ( Qing Ri Jin ),강원구 ( Won Ku Kang ),이종화 ( Jong Hwa Lee ),하정헌 ( Jung Heun Ha ),정은주 ( Eun Ju Jeong ) 한국약제학회 2007 Journal of Pharmaceutical Investigation Vol.37 No.3
SB-31의 Glycyrrhizin을 지표로 한 Rat과 Rabbit에서의 약물동태 및 심혈관계에 대한 연구
강원구,박용순,이동흠,권광일 충남대학교 약학대학 의약품개발연구소 1999 藥學論文集 Vol.15 No.-
SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rat's and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingredient for the pharmacokinetics of SB-31. The rat`s blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were 98.06±6.07ml, 0.33±0.05hr^-1 and 65.46±11.19ml, 0.68±0.25hr^-1, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were 235.24±30.72ml, 0.13±0.36 hr-1 and 341.32±28.58ml, 0.27±0.04 hr^-1, respectively. "WinNonlin" was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of 1/y-2. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (-dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about 6.9~11.5%. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.
플루옥세틴 캅셀제의 지원자에 대한 생체이용율 및 대사율 비교
강원구,박용순,조규행,최준식,권광일 충남대학교 약학대학 의약품개발연구소 1998 藥學論文集 Vol.14 No.-
Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake. This study was carried out to compare the bioavailability of Myung-in fluoxetine (20 ㎎/cap with that of Prozac?. The bioavailability was conducted on 24 healthy volunteers who received a single dose (80 ㎎) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 48 hours. plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters (AUC_0-48hr, Cmax, Tmax. AUC_inf.. MRT. T_1/2. Vd and Cl) were clculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program. "WinNonlin' was used for compartmental analysis. A two-compartment model with first-order inpot, first-order output and no lag time was chosen as the most appropriate phamacokinetic model. The data were best described by using a weighting factor of 1/y^2. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac® at all observed time from 7.9% to 16.9% (P<0.05 at 6, 7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac®. There were no statistical significant differences between the two drugs in al pharmacokinetic parameters including AUC_0-48hr of norfluoxetine.
Clarithromycin 정제의 생물학적 동등성 및 약물동태
강원구,박선영,박용순,우종수,최경업,권광일 충남대학교 약학대학 의약품개발연구소 1999 藥學論文集 Vol.15 No.-
This study was carried out to compare the bioavailability of Hanmi clarithromycin (250mg/tablet) with that of Klaricid®. The bioavailability was examined on 20 volu nteers who received a single dose (500mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 12 hours. Plasma samples were analyzed for clarithromycin and roxithromycin(internal standard) by HPLC/Coulometric ECD. The pharmacokinetic parameters (AUC_0-12h, Cmax, Tmax, AUC_inf, Ka, Kel, t_12, Vd/F and Cl/F) were calculated from the plasma clarithromycin concentration-time data of each volunteer. The computer program “WinNonlin” was used for compartmental analysis. One compartment model with first-order input, first-order output with lag time, weighting factor 1/y2 was chosen as the appropriate pharmacokinetic model. The major pharmacokinetic parameters (AUC_0-12h, AUC_inf, Cmax and Tmax) of Hanmi clarithromycin were 10.7±0.5μg·hr·ml^-1, 12.7±0.7μg·hr·ml^-1, 1.7±0.1μg/ml and 2.0±0.2hr, respectively, and those of Klaricid(R) were 9.8±0.5μg·hr·ml^-1, 11.7±0.6μg·hr·ml^-1, 1.6±0.1μg/ml and 2.1 ±0.1hr, respectively. The differences in mean values of AUC_0-12hr, AUC_inf and Cmax between two products were 9.88%, 8.94% and 6.59%, respectively. The least significant differences at alpha=0.05 for AUCO-12h, AUCinf and Cmax were 16.08%, 17.81% and 18.94%, respectively. Though the plasma clarithromycin concentrations of Hanmi clarithromycin were higher than those of Klaricid® at all observed times, the bioavailability of Hanmi clarithromycin appeared to be bioequivalent with that of Klaricid®. The Ka, Kel, t_1/2, Vd/F and Cl/F of the Hanmi clarithromycin were 2.69±0.53hr^-1, 0.18±0.01hr^-1, 3.9hr, 248.8±11.4L and 43.7±2.6L/hr, respectively, and those of Klaricid® were 2.19±0.51hr^-1, 0.18±0.02hr^-1, 3.7hr, 266.7±22.4L and 45.3±2.8L/hr, respectively. There were no statistically significant differences between two drugs in all pharmacokinetic parameters.
지원자의 Cefixime캅셀제 생체이용율에 대한 생물학적동등성 연구
강원구,우종수,권광일 충남대학교 약학대학 의약품개발연구소 1998 藥學論文集 Vol.14 No.-
Cefixime is an orally absorbed 3rd generation cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and is highly resisitant to β-lactamase degradation. This study was carried out to evaluate the bioavailability of a new test drug of cefixime (100 ㎎/capsule) relative to the reference drug. The bioavailability was conducted on 20 healthy volunteers who received a single dose (400 ㎎) of the test and the reference drugs in the fasting state, in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 12 hours. Plasma was analyzed for cefixime by a sensitive and validated HPLC assay. The major phamacokinetic parameters (AUC_0-12hr, C_max, T_max) were calculated from the plasma concentration-time data of each volunteer. The AUC_0-12hr, C_max, and T_max of the test drug were 36.91±11.85 ㎍·hr/㎖, 5.47±1.61 ㎍/㎖, and 4.00±0.65 hr, respectively, and those of the reference drug were 34.08±8.81 ㎍·hr/㎖, 5.25±1.40 ㎍/㎖, and 4.20±0.62 hr, respectively. Mean differences of those parameters were 8.32, 4.29, and 4.76%, respectively, and the least significant differences at α=0.05 for AUC_0-12hr, C_max, T_max were 16.02, 13.78, and 11.76%, respectively. In conclusion, the test drug was bioequivalent with the reference drug. (Kor. J. Clin. Pharm. 1998;8(1): 19-22)