• 한국임상약학회지
• /
• 제28권1호
• /
• pp.24-29
• /
• 2018

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

• 대한치과의사협회지
• /
• 제15권2호
• /
• pp.145-151
• /
• 1977

The author performed Snyder test, estimation of salivary flow rate, salivary viscosity test, salivary buffering capacity test, M-R test, oral hygiene ability test, estimation of oral glucose clearance time and plaque reformation test in the 107 male Koreans aged form the age of 20 to 29, in order to detect and control the active cariogenic factors contributing to caries development on the individual basis. Thereafter, the data from 8 kinds of caries activity test were analysed and evaluated. The obtained results were as follows: 1. Snyder test was positive in 86.0% of total tested persons, and among those showing positive Snyder test reaction, slight caries activity was appeared in 39.1%, moderate caries activity in 23.9%, and marked caries activity in 37.0%. 2. Salivary flow rate was under the average flow amount in 53.3%. 3. Salivary buffering capacity was low in 22.4%. 5. Buffering capacity of dental plaque was high in 12.5%. 6. Oral hygiene ability was insufficient in all persons tested. 7. Oral glucose clearance time was long in 42.1%. 8. Plaque reformation rate was high in 8.4% of the 107 persons tested.

• Journal of Microbiology and Biotechnology
• /
• 제20권10호
• /
• pp.1463-1470
• /
• 2010

E. coli has long been widely used as a host system for the manufacture of recombinant proteins intended for human therapeutic use. When considering the impurities to be eliminated during the downstream process, residual host cell DNA is a major safety concern. The presence of residual E. coli host cell DNA in the final products is typically determined using a conventional slot blot hybridization assay or total DNA Threshold assay. However, both the former and latter methods are time consuming, expensive, and relatively insensitive. This study thus attempted to develop a more sensitive real-time PCR assay for the specific detection of residual E. coli DNA. This novel method was then compared with the slot blot hybridization assay and total DNA Threshold assay in order to determine its effectiveness and overall capabilities. The novel approach involved the selection of a specific primer pair for amplification of the E. coli 16S rRNA gene in an effort to improve sensitivity, whereas the E. coli host cell DNA quantification took place through the use of SYBR Green I. The detection limit of the real-time PCR assay, under these optimized conditions, was calculated to be 0.042 pg genomic DNA, which was much higher than those of both the slot blot hybridization assay and total DNA Threshold assay, where the detection limits were 2.42 and 3.73 pg genomic DNA, respectively. Hence, the real-time PCR assay can be said to be more reproducible, more accurate, and more precise than either the slot blot hybridization assay or total DNA Threshold assay. The real-time PCR assay may thus be a promising new tool for the quantitative detection and clearance validation of residual E. coli host cell DNA during the manufacturingprocess for recombinant therapeutics.

• Biomolecules & Therapeutics
• /
• 제30권6호
• /
• pp.510-519
• /
• 2022

Tofacitinib, a Janus kinase 1 and 3 inhibitor, is mainly metabolized by CYP3A1/2 and CYP2C11 in the liver. The drug has been approved for the chronic treatment of severe ulcerative colitis, a chronic inflammatory bowel disease. This study investigated the pharmacokinetics of tofacitinib in rats with dextran sulfate sodium (DSS)-induced ulcerative colitis. After 1-min of intravenous infusion of tofacitinib (10 mg/kg), the area under the plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib significantly increased by 92.3%. The time-averaged total body clearance decreased significantly by 47.7% in DSS rats compared with control rats. After the oral administration of tofacitinib (20 mg/kg), the AUC increased by 85.5% in DSS rats. These results could be due to decreased intrinsic clearance of the drug caused by the reduction of CYP3A1/2 and CYP2C11 in the liver and intestine of DSS rats. In conclusion, ulcerative colitis inhibited CYP3A1/2 and CYP2C11 in the liver and intestines of DSS rats and slowed the metabolism of tofacitinib, resulting in increased plasma concentrations of tofacitinib in DSS rats.

• 대한약리학회지
• /
• 제25권1호
• /
• pp.101-107
• /
• 1989

Procainamide를 투여후 이 약물 및 활성형 대사산물인 N-acetylprocainamide (NAPA)의 약동학적 성상을 알아보기 위해 숫컷 성견 5마리에 procainamide 및 NAPA를 교차 투여하여 얻은 혈장농도 data를 2-compartmental model에 의해 약동학적 분석을 시행하여 다음과 같은 결과를 얻었다. 1. 10mg/kg의 procainamide를 1회 15분간 정주후 혈장 procainamide 농도변화는 명백한 분포기와 소실기를 보였으며 생성된 NAPA의 혈장농도는 시간경과에 따라 최고혈장농도는 $0.124{\mu}g/ml$ 이하이었으며 정주 직후 조직분포에 따른 혈장농도의 일시적으로 감소 후 증가하는 초기 dip 현상을 보였다. 2. Procainamide의 steady-state 분포용적(Vss) 및 central compartment volume (Vc)은 각각 $1.20{\pm}0.27\;L/kg$ 및 $0.36{\pm}0.08\;L/kg$ 이였으며 NAPA의 Vss및 Vd는 $1.21{\pm}0.21\;L/kg$ 및 $0.26{\pm}0.07\;L/kg$이었다. 3. Procainamide 및 NAPA의 청소율(Cl)은 각 $0.47{\pm}0.08\;L/kg/hr$와 $0.35{\pm}0.08\;L/kg/hr$ 이었으며 혈장 반감기$(t_{1/2{\beta}})$는 각각 2.85 및 2.77 시간이었다. 4. N-acetylation에 의한 Procainamide의 대사청소율은 $18.24{\pm}6.22\;ml/kg/hr$로 이는 전체 procainamide 청소율의 3.9%를 차지하였다.

• 한국임상약학회지
• /
• 제9권1호
• /
• pp.55-61
• /
• 1999

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride treatment when aminophylline (8 mg/kg as theophylline, i.v.) was injected. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes was determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to $17\%$ of the control value while AUC (area under the plasma concentration-time curve) and $(t_{1/2})_{\beta}$ were increased to about 6 fold and 10 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to $33-41\%$ of the control value in microsomes of cirrhotic rat liver. From these results, it can be concluded that in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride the total body clearance of theophylline is markedly reduced due to a reduced hepatic metabolism.

• 한국임상약학회지
• /
• 제11권2호
• /
• pp.57-61
• /
• 2001

The effect of circadian rhythm on the pharmacokinetics of acebutolol was studied in rabbits administered intravenous 5 mg/kg dose of acebutolol at 09:00 in the morning (a.m) and 22:00 in the evening (p.m). A significant effect of circadian rhythm of pbarmacokinetic parameters as a function of time of day was noted in rabbits, showing lower total body clearance (CLt), higher plasma concentration and the area under the plasma concentration time curve (AUC) when acebutolol was given in the evening. The plasma concentration of acebutolol was increased significantly (p<0.05) at 12-24 hr after dosing in the evening. The AUC was greater in the evening $(111\%)$ than that in the morning and $CL_t$, was higher when acebutolol was given in the morning ($1.12\pm0.24$ ml/hr) versus in the evening ($1.01\pm0.22$ ml/hr), but those were not significant. Therefore, It is reasonable to consider individual circadian rhythm for effective dosage regimen of acebutolol in clinical chronotherapeutics.

• Journal of Electrical Engineering and Technology
• /
• 제9권1호
• /
• pp.71-79
• /
• 2014

This paper discusses a method for the determination of frequency control reserve requirement with consideration of the interaction between ex-ante planning and real-time balancing. In proposed method, we consider the fact that the delivered energy for tertiary control reserve is determined based on required capacity for secondary control reserve and the expected amount of load errors. Uncertain load errors are derived by Brownian motion, an optimization method is suggested using a stochastic programming. In a short, we propose an interactive dependent method for determining secondary control reserve requirement based on the principle that it satisfies to minimize the total cost. As a result, this paper provides will analyze for an example model to demonstrate the capabilities of the method.

• 생태와환경
• /
• 제39권3호통권117호
• /
• pp.390-401
• /
• 2006

2005년 4월부터 12월까지 팔당호 생태계에서 식물플랑크톤 동물플랑크톤 간의 영양적 관계를 파악하기 위하여 플랑크톤 구조 분석과 섭식실험을 실시하였다. 동물플랑크톤은 소형 (MICZ: 60{\sim}20\;{\mu}m$)과 대형동물플랑크톤 (MACZ: >$200\;{\mu}m$)으로 구분하며 각기 식물플랑크톤에 대한 여과율과 탄소전달율을 측정하였다. 섭식실험은 현장 동물플랑크톤의 0, 2, 4, 8배로 농도 차이를 두어 2회 반복 실험을 실시하였다. 두 지점에서 식물플랑크톤 군집은 규조류 (Aulacoseira, Cyclotella )가 수적으로 우점하였으나, 탄소생물량은 편모조류 (Cryptomonas ovata)가 높았다. 두 지점 모두 동물플랑크톤 군집 내에서 윤충류 (Brachionus, Keratella, Polyathra)가 수적으로 크게 우점하였으나, 탄소생물량은 지각류 (Daphnia)가 가장 높았다. 동물플랑크톤은 봄에 높은 밀도와 탄소생물량을 보였고 여름철 집중강우 시기를 기점으로 크게 감소하였다. 지점별로는 경안천에서 상대적으로 높은 탄소생물량이 나타났다. 동물플랑크톤 여과율과 탄소전달율은 두 지점 모두 봄 동안에 높았으나 여름 이후에 낮아졌으며, 탄소전달율의 변화는 동물플랑크톤 생물량의 변화와 유사하게 나타났다. 군집여과율과 식물플랑크톤에 대한 탄소전달율은 MACZ가 MICZ보다 높았고, 그 정도는 경안천에서 더 높게 나타났다. 여름철의 집중강우로 인한 짧은 체류시간과 수체의 교란이 동물플랑크톤의 섭식에 영향을 미치는 것으로 파악되었다.

• Journal of Pharmaceutical Investigation
• /
• 제38권3호
• /
• pp.151-155
• /
• 2008

Circadian variations of acebutolol and its main metabolite, diacetolol pharmacokinetics were studied after a single oral administration of acebutolol (10 mg/kg) to eight rabbits at 10 : 00 AM (in the morning) and 10 : 00 PM (at night). The plasma concentration profiles of acebutolol were significantly different (P<0.05) between 10 : 00 AM and 22 : 00 PM, suggesting circadian variations of pharmacokinetic behaviors. A significant circadian rhythm of pharmacokinetic parameters was noted in rabbits, showing higher total body clearance (CL/F), and lower the area under the plasma concentration-time curves (AUC) of acebutolol than that at night. The half-life ($t_{1/2}$) of acebutolol and diacetolol were also significantly shorter in the morning than at night (P<0.05). Metabolite-parent AUC ratio at night significantly decreased compared to in the morning, implying that night time could inhibit acebutolol metabolism than in the morning. From this study there was an administration-time difference of acebutolol pharmacokinetics in the rabbits. The optimized dosing regimen of acebutolol can be decided by considering circadian rhythm so that the effective therapies are established for patients.