향류마치스 효과를 갖는 새로운 히스톤 Hl 단백질 (p961)의 횐쥐와 토끼에 대한 약물동태

우수경(Su Kyung Woo),윤민혁(Min Hyuk Yun),이재홍(Jae Heung Lee),권광일(Kwang Il Kwon) 대한약학회 2001 약학회지 Vol.45 No.4

A purified histone Hl protein, p961, which plays a role in mediating the condensation of DNA into chromatin, was recently proved as an arthritis-suppressing agent in the mouse CIA model. The pearmacokinetics of p961 was carried out in rats and rabbits. The rat's blood, bile and urine samples were semially collected from the femoral vein, common bile duct, and bladder respective1y; after bolus I.v. injection at low (10 mghg) and high (30 mg/mg) doses. The rabbit's blood samples were also collected from the marginal ear vein after bolus I.Y. injection at a dose 10 mg/kg. P961 and its major metabolite in the physiological samples were analyzed by reverse-phase HPLC using a Vydac C4 protein column and a multistep water-acetonitrile gradient containing 0.24% trifluoroacetic acid. The major pharmacokinetic parameters (AUC, Cmax, MRT t1/2, Vss and Cl) were estimated from the time course of plasma p961 and metabolite concentrations using WinNonlin. A two- compartment model was chosen for p961 as the most appropriate pharmacokinetic model. After I.v, injection of p961 at doses of 10 mghg and 30 mg/kg, more than 80% of p961 was removed rapidly from the plasma within 15 min. The plasma half-life of p961 in rats and rabbits was found not to exceed 12 min. p961 (22448.9 mot wt) was rapidly cleaved to 21612 mol wt fragment and the breakdown product appeared rapidly in the circulation with no lag phase. P961 and metabolite were not detected in rat urine and bile.

토양여과를 묘사하는 다단층 여과장치를 이용한 대용량 하천수질 정화 설비 기초연구

김호석 ( Hoh Seok Kim ),김기팔 ( Ki Par Kim ),윤민혁 ( Min Hyuk Yun ),신재원 ( Jae Won Shin ),김성진 ( Sung Jin Kim ),허갑수 ( Gap Su Huh ),안규홍 ( Kyu Hong Ahn ) 한국물환경학회 ( 구 한국수질보전학회 ) 2012 한국물환경학회·대한상하수도학회 공동 춘계학술발표회 Vol.2012 No.-

Tacrolimus의 LC/MS 분석과 지원자에 대한 약물동태 연구

윤민혁,이서판,남진경,권광일 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

The purpose of this study was to confirm the analysis method and also to estimate the pharmacokinetic parameters of tacrolimus in human volunteers. The pharmacokinetics of tacrolimus tablet was examined on 24 healthy volunteers who received a single oral dose(4mg) of each preparation in the fasting state. After an oral dosing, blood samples were collected for a period of 72 hours. Blood concentrations of tacrolimus were determined using a liquid chromatographic electrospray mass spectrometric (LC-MS) method. The pharmacokinetic parameters were calculated with non-compartmental(AUC, C_(max), T_(max), Cl_(t), V/F) and compartmental(K_(el), K_(a), K_(12), K_(21), t_(1/2)) pharmacokinetic analysis using WinNonlin program. The estimated means of AUC_(0-72hours), C_(max) and T_(max) were 425.54 ± 197.49 ng·hr/ml, 76.14 ± 29.18 ng/ml and 1.40 ± 0.44 hr, respectively. The means of other pharmacokinetic parameters(V/F, CL_(t), K_(el), K_(a), K_(23), K_(32) and t_(1/2)) were 35.12 ± 34.28 L, 10.45 ± 5.32 L/hr, 0.39 ± 0.21 hr^(-1), 1.91 ± 4.17 hr^(-1), 0.32 ± 0.33 hr^(-1), 0.07 ± 0.09 hr^(-1), 26.94 ± 10.19 hr^(-1), respectively.

퀴니딘 정제의 건강한 한국인에 대한 약물동태

박희찬,윤민혁,김동출,권준택,권광일 충남대학교 약학대학 의약품개발연구소 2004 藥學論文集 Vol.19 No.-

The purpose of this study was to estimate the pharmacokinetics of quinidine sulfate in healthy Korean The parameters were examined on 16 volunteers who received a oral single dose(200mg quinidine sulfate). After dosing. blood samples were collected for a period of 24 hours. Plasma samples were analyzed for quinidine sulfate and DL-propranolol hydrochloride(internal standard) by HPLC/UV. The pharmacokinetic parameters (AUC_(0-24hr), AUC_(inf). C_(max), T_(max), K_(a), K_(el), t_(1/2), Vd/F and Cl/F) were calculated from the plasma quinidine sulfate 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 was chosen as the appropriate pharmacokinetic model. The pharmacokinetic parameters(AUC_(0-24hr). AUC_(inf). C_(max), T_(max), K_(a), K_(el), T_(1/2), Vd/F and Cl/F) calculated 9.47±2.24 ㎍·hr·㎖^(-1), 10.95±2.62 ㎍·hr·㎖^(-1), 0.93±0.16 ㎍/㎖, 1.56±0.45 hr, 1.10±0.36 hr^(-1), 5.17+0.90 hr, 162.38±33.36 L and 22.27±5.35 L/hr, respectively.

인체에서 carvedilol의 심혈관계 작용에 대한 PK/PD modeling

백인환,윤민혁,윤휘열,남진경,권광일 충남대학교 약학대학 의약품개발연구소 2007 藥學論文集 Vol.22 No.-

The objective of the present study was to determine and characterize the relationship between the cardiovascular effect and plasma concentration of carvedilol by PK/PD modeling in human. A group of 32 healthy males received oral doses of 25 mg carvedilol, and blood samples were collected thirteen times for up to 30 hours after the drug administration. The effect of carvedilol on blood pressure was measured during the same period. This experiment was analyzed using the liquid-liquid extractions of carvedilol by HPLC with fluorescence detection. Pharmacokinetics parameters of carvedilol were calculated using the two-compartment model with first-order absorption. The average value of C_(max), T_(max), CL/F (apparent clearance), V/F (apparent volume of distribution) and half-life of carvedilol were 62.74 ± 20.12 ng/ml, 1.26 ± 0.86 hrs, 94.64 ± 46.01 L/hr, 1561.78 ± 941.94 L, 12.47 hr, respectively. To explain the relationship between the cardiovascular effect and plasma concentration of carvedilol, plasma drug concentrations were linked to the observed SBP and DBP via a effect compartment with a sigmoid Emax model. The model parameters were estimated by using ADAPT Ⅱ program. This PK/PD model could describe the relationship between plasma concentrations of carvedilol and cardiovascular effect such as the aspects of decreasing blood pressure and the time delay between plasma concentration and pharmaco-dynamic data.

LC/MS/MS 분석법을 이용한 Amlodipine의 약물동태연구

서정원,윤민혁,강원구,권광일 충남대학교 약학대학 의약품개발연구소 2007 藥學論文集 Vol.22 No.-

The aim of this study were to confirm the analysis method and also to estimate the pharmacokinetic parameters of amlodipine in human volunteers. In an open-label single-dose pharmacokinetic study, a group, consisting of 24 healthy volunteers, received single oral dose of 5mg amlodipine. Blood sample were taken for up to 120 hours. The concentration of amlodipine in these body fluids was determinated using a validated high-performance liquid chromatography(HPLC) method with tandem mass spectrometry. Amlodipine and ketoconazole, an internal standard, were extracted from plasma using ethyl acetate in the presence of 0.1M sodium carbonate. After drying the organic layer, the residue was reconstituted in mobile phase(acetonitrile : water = 70 : 30 v/v (0.1% formic acid)) and injected onto a Zorvax C18 column (2.1 × 100 mm, 3.5 ㎛ particles). The isocratic mobile phase was eluted at 0.2ml/min. The ion transitions monitored in multiple reaction-monitoring mode were m/z 410.10 → 294.95 and 532.11 → 81.95, respectively. The coefficient of variance of the assay precision was less than 12%, and the accuracy exceeded 99.1%. The limit of quantification was 0.1 ng/ml. The pharmacokinetic parameters were calculated with non-compartmental(AUC, C_(max), T_(max), CL_(t), V/F) and compartmental(K_(el), K_(a), t_(lag)) pharmacokinetic analysis using WinNonlin program. The estimated means of AUC_(0-120hr), C_(max) and T_(max) were 196.90 ± 5.02 ng·hr/ml, 3.36 ± 0.09 ng/ml and 10.44 ± 0.61 hr, respectively. The means of other pharmacokinetic parameters(V/F, CL_(t), K_(el), K_(a) and t_(lag)) were 1208.06 ± 50.61 L, 25.39 ± 0.65 L/hr, 0.2806 ± 0.0294 hr^(-1), 0.0210 ± 0.0008 hr-1 and 0.4574 ± 0.0635 hours, respectively.