http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
유선동 한국독성학회 2002 Toxicological Research Vol.18 No.4
Toxicokinetic studies are intended to provide critical evaluation of drug disposition at toxicological doses and help understand the relationship between blood or tissue levels and the time course of toxic events. Relatively high dose levels used in toxicokinetics, compared to pharmacokinetics, complicates absorption, protein binding, metabolism and elimination processes. In this mini review, frequently used toxicokinetic models such as linear compartment medels, physiological models, and nonlinear kinetic models are introduced. In addition, optimization of toxicokinetic studies, their role in the drug development process, and prediction of human toxicokinetics based on animal data by interspecies scaling are briefly discussed.
임현균,유선동,김경호,한상범,염정록,Lim, Hyon-Kyun,Yoo, Sun-Dong,Kim, Kyeong-Ho,Han, Sang-Beom,Youm, Jeong-Rok 대한약학회 2007 약학회지 Vol.51 No.2
A simple and sensitive HPLC-MS method for quantitation of 10${\alpha}$-methoxy-9,10-dihydrolysergol (MDL), the main metabolite of nicergoline, in human plasma was developed and the bioavailability parameters of MDL was assessed in Korean healthy male volunteers. Clomipramine was used as an internal standard. MDL and internal standard in plasma sample were extracted using ethyl acetate. A centrifuged upper layer was then evaporated and reconstituted with mobile phase of 10 mM ammonium acetate-acetonitrile (10 : 90, v/v). The reconstituted samples were injected into a Zorbax SB-C8 column (2.1${\times}$150 mm,5 ${\mu}$m) at a flow-rate of 0.3 ml/min. Using MS with selected ion monitoring (SIM) mode, MDL and clomipramine were detected without severe interference from human plasma matrix. MDL produced a protonated molecular ion ([M+H]$^+$) at m/z 287. Internal standard produced a protonated molecular ion ([M+H]$^+$) at m/z 315. A linear relationship for MDL was found in the range of 2.5${\sim}$100 ng/ml. The lower limit of quantitation (LLOQ) was 2.5 ng/ml with acceptable precision and accuracy. The intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. Main pharmacokinetic parameters of 30 mg of nicergoline were revealed as follows: AUC$_t$ 321.1${\pm}$64.5 ng${\cdot}$hr/ml, C$_{max}$, 51.2${\pm}$25.3 ng/ml, T$_{max}$ 3.6${\pm}$1.5 hr, K$_{el}$ 0.12${\pm}$0.07 hr$^{-1}$ and t$_{1/2}$ 7.6${\pm}$3.4 hr. Inter subject variations and race differences were shown in comparison with the published data in the literature.
지혜영,신범수,박은정,박은석,유선동,이혜숙,정동원 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.2
This study was conducted to predict the pharmacokinetics of oleanolic acid in humans based on animal data by allometry and several species-invariant time methods. Oleanolic acid was injected intravenously to mice, rats, rabbit and dogs (dose 1 mg/kg). The serum concentration-time profiles of oleanolic acid were best described by bi-exponential equation in all animal species. The average Cl, Vss and t1/2 were 0.065 L/h, 0.019 L and 28.7 min in mice, 0.47 ± 0.06 L/h, 0.117 ± 0.029 L and 29.7 ± 12.2 min in rats, 2.77 ± 0.88 L/h, 1.83 ± 0.60 L and 84.4 ± 16.9 min in rabbits and 14.0 ± 0.7 L/h, 9.2 ± 10.1 L and 54.5 ± 57.2 min in dogs, respectively. Based on animal data, human pharmacokinetic parameters of Cl, Vss and t1/2 were predicted by simple allometry. In addition, actual concentration-time profiles obtained from animals were transformed to human profiles by species-invariant times of kallynochron, apolysichron and dienetichron. The predicted human pharmacokinetic parameters of Cl, Vss and t1/2 by using simple allometry and species-invariant time transformation method ranged from 48.3-97.2 L/h, 49.1-92.9 L and 45.6–187.2 min, respectively. Those predicted parameters of oleanolic acid may be useful in designing dosing schedules of oleanolic acid in future clinical studies.
Pharmacokinetics and Tissue Distribution of Psammaplin A, a Novel Anticancer Agent, in Mice
김학재,김태환,서원식,유선동,김일한,주상훈,신소영,박은석,마은숙,신범수 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.10
This study reports the pharmacokinetics and tissue distribution of a novel histone deacetylase and DNA methyltransferase inhibitor, psammaplin A (PsA), in mice. PsA concentrations were determined by a validated LC-MS/MS assay method (LLOQ 2 ng/mL). Following intravenous injection at a dose of 10 mg/kg in mice, PsA was rapidly eliminated, with the average half-life (t1/2, λn) of 9.9 ± 1.4 min and the systemic clearance (CLs) of 925.1 ± 570.1 mL/min. The in vitro stability of PsA was determined in different tissue homogenates. The average degradation t1/2 of PsA in blood, liver, kidney and lung was found relatively short (≤ 12.8 min). Concerning the in vivo tissue distribution characteristics, PsA was found to be highly distributed to lung tissues, with the lung-to-serum partition coefficients (Kp) ranging from 49.9 to 60.2. In contrast, PsA concentrations in other tissues were either comparable with or less than serum concentrations. The high and specific lung targeting characteristics indicates that PsA has the potential to be developed as a lung cancer treatment agent.
Pharmacokinetics of Magnolin in Rats
Nam Jin Kim,Won Young Song,유선동,Hyeong-Kyu Lee,오세량,Hye Suk Lee 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.6
This study was first conducted to characterize the intravenous and oral pharmacokinetics of magnolin, a major pharmacologically active ingredient of Magnolia fargesii, at various doses in rats. Magnolin was administered to rats by intravenous injection (0.5, 1 and 2 mg/kg doses) and oral administration (1, 2 and 4 mg/kg doses), and serial plasma and urine samples were harvested. Magnolin concentrations were determined by a validated LC/MS/MS assay. After both intravenous and oral administration, the AUCs were linearly increased as the dose increased. Other pharmacokinetic parameters of magnolin (except the Vss after the intravenous administration) were also independent of the doses. The extent of absolute oral bioavailability ranged from 54.3-76.4% for the oral doses examined. Magnolin was considerably bound to rat plasma proteins and the binding value was constant (71.3-80.5%) over a concentration ranging from 500 to 10000 ng/mL. The pharmacokinetic parameters of magnolin were doseindependent after both intravenous and oral administration. When given orally, magnolin was rapidly absorbed.
권민창,염대일,김남아,최두형,박준상,왕훈식,유선동,정성훈 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.1
This study was to evaluate the pharmacokineticsand bioequivalence of two tacrolimus formulationswhich had different in vitro drug release profiles. Dynamicsolubility, in vitro dissolution profiles of the two formulations,and their influence on pharmacokinetics wereexamined. The male volunteers were randomly assigned toreceive a single 1-mg capsule of the test or reference formulationand pharmacokinetic parameters were determinedusing a noncompartmental method. The two formulationsreleased [85 % of tacrolimus in water within 30 min,which passed the criterion of evaluating the test formulation. However, the test formulation produced a faster initialrelease rate and plateaued in about 15 min, while the referenceshowed almost zero order initial release profiles. The AUC0-? values were 145.92 (reference) and140.49 ng h/mL (test). The mean Cmax was 15.70 (reference)and 16.08 ng/mL (test) with Tmax values of 1.63 and1.60 h, respectively. The t1/2 for the reference and testformulations was 29.12 and 27.85 h, respectively. Relativebioavailability was calculated to be 96.28 %. The pointestimates for the mean ratio of the test to reference for theAUC0-t and Cmax were 0.969 and 1.026, respectively,satisfying the criterion for bioequivalence. The resultssuggest that the test formulation is pharmacokineticallyequivalent to the reference in terms of both rate and extentof absorption. Even though the in vitro dissolution profilesof the formulations might not be equivalent, the pharmacokineticsindicated bioequivalence. Therefore, whendeveloping poorly soluble drugs, it might be beneficial topay attention to the dynamic solubility as well as dissolution profiles.