http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
완전 모형 추정법을 이용한 임상적으로 유의한 공변량 평가
윤휘열 충남대학교 약학대학 의약품개발연구소 2014 藥學論文集 Vol.29 No.-
Adding covariates to model parameter using stepwise method are able to lead to covariate selection bias. Full model approach, which was allowing all relationships between parameters and covariates, were developed recently for improvement of selection bias. The main objective of this study was to evaluate covariates effect focused on clinical aspects using full model approach. A semi-mechanistic myelosuppression model with four structural parameters and a dataset containing 636 individuals and 3549 observations was used. The performance was evaluated in terms of model estimates and precision of parameters and ability to identify clinically relevant covariates. FOCE-I with NONMEM 7.2 assisted by PsN was used. Full model approach were successfully implemented, also good agreement in comparison with previous stepwise study, were found to be identified the same parameter-covariate relationships to be clinically relevant. Although full model approach and stepwise study performed equally well for finding covariates, however, full model approach has advantages in comparison with traditional methods when investigating clinically relevant covariates and minimize for statistical error.
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.
Afloqualone의 LC/MS/MS분석과 건강한 성인 지원자에 대한 약물동태 연구
이서판,이병요,윤휘열,이은주,권광일 충남대학교 약학대학 의약품개발연구소 2008 藥學論文集 Vol.23 No.-
Afloqualone is a centrally acting muscle relaxant that inhibits mono- and polysynaptic reflexes. The purpose of this study was to estimate the pharmacokinetic parameters of afloqualone in healthy volunteers. The pharmacokinetics of afloqualone tablet was examined on 24 healthy volunteers who received a single oral dose(20 Bg) of each preparation in the fasting state. Blood samples were ten at 0, 0.5, 1, 1.5 2 3 4 6 8 10, 12 and 24 hr after drug administration. Blood concentrations of afloqualone were determined using a liquid chromatography tandem mass spectrometry(LC/MS/MS) systems. A two compartment model was used to explain the pharmacokinetic properties of afloqualone. The pharmacokinetic parameters were calculated with model independent(AUC, C_max, T_max, CL_t, V/F) and model dependent(K_ei, K_a, K_cp, K_pc, t_1/2) Pharmacokinetic analysis using WinNonlin program. The estimated means of AUC_0-24hours, C_max, T_max CL_t and V/F were 148.99 ± 127.39 ng·hi/ml 35.11 ± 56.62 ng/ml, 1.81 士 1.34 hr, 189.01 士 79.67 L/hr and 848.61 ± 567.06 L, respectively. The model dependent parameters(K_ei, K_a, K_cp, K_pc, t_1/2) were 0.14 ± 0.18 hr^(-1), 11.64 ± 30.03 hr^(-1), 0.34 ± 0.39 hr^(-1), 0.1 ± 0.16 hr^(-1) and 10.56 ± 4.30 hr, respectively. In conclusion a two compartment model was best described the pharmacokinetic behavior of afloqualone in healthy human.
혈소판 응집 억제제의 효과 측정법에 대한 고찰과 지원자에서 Triflusal의 혈소판 응집 억제능 평가
이병요,장힘찬,백인환,윤휘열,권광일 충남대학교 약학대학 의약품개발연구소 2010 藥學論文集 Vol.25 No.-
The anti-platelet agent is a member of a class of pharmaceuticals that decreases platelet aggregation and inhibits thrombus formation. They are effective in the arterial circulation and widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease. As a method for estimating the effects of anti-platelet agent, platelet aggregation was conventionally measured using the optical method or the impedance method. Several alternate methods currently in development or recently developed were considered, including luminescence method, flow cytometry, laser-light scattering method, and Verify Now-P2Y12 assay. Principles, advantages, and disadvantages of the optical method, impedance method, and the other alternate platelet aggregation methods were discussed in this report. 15 human volunteers were recruited for the evaluation of the efficacy of triflusal using the optical method. After the oral administration of a single dose of 900mg, 15 subjects received eight doses administered at 24-hour intervals of 600mg triflusal. Using platelet rich-plasma from above subjects, we performed baseline platelet aggregation test induced by adenosine diphosphate(ADP), collagen, and arachidonic acid. The results of platelet aggregation test after triflusal administration were compared with the baseline study. Triflusal significantly inhibited platelet aggregation induced by ADP (33.0±21.3%) and arachidonic acid (99.1±1.2%), respectively. Therefore, we concluded that anti-platelet aggregation effect of triflusal can be studied successfully with the optical method. Each of the platelet aggregation methods has value for evaluating the effects by various mechanisms of the anti-platelet agents. The ideal method for estimating the platelet aggregation as it relates to safety and efficacy in patients treated with anti-platelet agents will need to be determined in clinical trials.
당뇨병 치료를 위한 SGLT2 억제제의 심혈관계 안전성 관련 최근 임상시험 결과고찰
김혜럼, 한나영, 유미선, 권광일, 윤휘열 충남대학교 약학대학 의약품개발연구소 2017 藥學論文集 Vol.32 No.-
Patients with type 2 diabetes have a two-to three-times greater risk of developing car-diovascular disease than people without diabetes, and the mortality rate from cardiovascular disease is also reported to increase. The reason why cardiovascular disease is more common in type 2 diabetic patients is not only that cardiovascular risk factors are more common than non-diabetic patients, but also that diabetes itself is an independent risk factor for cardiovascular disease. Since rosiglitazone. which was introduced as a treatment for type 2 diabetes in 2000, has been argued to increase cardiovascular disease sluch as myocardial infarction. there were clinical trials of cardiovascular safety of it such as DREAM. ADOPT and RECORD. As a result. rosiglitazone has been banned due to the risk of cardiovascular disease. The US FDA and other regulatory agencies have required clinical trials for type 2 diabetes treatments afterward. 1n this study. it is reviewed that recently developed SGL T2 inhibitors has cardiovascular benefits as a novel mechanism of type 2 diabetes treatment. SGL T2 inhibitors inhibit the renal sodium glucose co-transporter(SGLT2), thereby reducing glucose reabsorption and increasing excretion of it. and consequently lowering blood glucose levels. Recent papers on ongoing cardiovascular-related clinical trials of SGL T2 in-hibitors such as CANVAS. CANVAS-R. CREDENCE of canagliflozin, DECLARE-TIMI 58 of dapagliflozin. and EMPA -REG outcomes of empagliflozin were examined thoroughly as well.
항히스타민제의 대리결과변수로서 히스타민에 의한 피내주사반응 유용성에 대한 고찰
한나영, 송병정, 백현문, 정에벤, 유영훈, 전지현, 구성우, 윤휘열, 권광일 충남대학교 약학대학 의약품개발연구소 2017 藥學論文集 Vol.32 No.-
In this study, it is reviewed that histamine-induced wheal and flare responses are potential sur-rogate endpoints for predicting the clinical effects of antihistamines in patients with allergic skin diseases. Histamine plays an important role in allergic response by inducing degranulation of mast cells due to allergen exposure and mediating the inflammatory reaction. Thus, suppression of histamine-induced wheal and flare has been noted as surrogate markers for efficacy of Hl receptor antagonists. In addition, allergy skin prick test and intradermal test using histamine have been used to diagnose the histamin-induced allergic reaction. However, it has been well known that allergic diseases are not only mediated by histamine. but also by var-ious immunological inflammatory responses. Previous studies reported that there is a lack of evidence about the correlation between antihistamines to predict clinical efficacy and antihistamine efficacy, although hista-mine-induced wheal and flare responses may be useful indicators of the dose-response relationship. In con-clusion, the evaluation for the suppression of wheal and flare after histamine injection is reasonable for de-termining the treatment of allergic simple skin diseases, but there is a limit to evaluate the efficacy in com-plex inflammatory diseases mediated IgE or T cells, or other immune complex. Therefore, further studies are needed to identify additional surrogate endpoints to predict the therapeutic effect of antihistamines in other inflammatory diseases such as allergic rhinitis, atopic conjunctivitis, allergic asthma, and so on.
Ahn, Ji Yun,Tae, Hyun-Jin,Cho, Jeong-Hwi,Kim, In Hye,Ahn, Ji Hyeon,Park, Joon Ha,Kim, Dong Won,Cho, Jun Hwi,Won, Moo-Ho,Hong, Seongkweon,Lee, Jae-Chul,Seo, Jeong Yeol Medknow PublicationsMedia Pvt Ltd 2015 Neural regeneration research Vol.10 No.8
<P>c-Fos is a good biological marker for detecting the pathogenesis of central nervous system disorders. Few studies are reported on the change in myocardial infarction-induced c-Fos expression in the paralimbic regions. Thus, in this study, we investigated the changes in c-Fos expression in the rat cingulate and piriform cortices after myocardial infarction. Neuronal degeneration in cingulate and piriform cortices after myocardial infarction was detected using cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining. c-Fos-immunoreactive cells were observed in cingulate and piriform cortices at 3 days after myocardial infarction and peaked at 7 and 14 days after myocardial infarction. But they were hardly observed at 56 days after myocardial infarction. The chronological change of c-Fos expression determined by western blot analysis was basically the same as that of c-Fos immunoreactivity. These results indicate that myocardial infarction can cause the chronological change of immediate-early response gene c-Fos protein expression, which might be associated with the neural activity induced by myocardial infarction.</P>