• Asian Pacific Journal of Cancer Prevention
• /
• 제16권8호
• /
• pp.3559-3563
• /
• 2015

The aim of the present study was to evaluate the relative contribution of CYP1A2 isoforms (-3860 G/A, -2467T/delT and -163C/A) in control subjects and breast cancer patients to the metabolism of caffeine in human liver. Restriction fragment length polymorphism analysis of PCR-amplified Fragments (PCR-RFLP) was used for the genotyping of CYP1A2 SNPs and HPLC allowed the phenotyping through the measurement of CYP1A2 activity using the 17X + 13X + 37X/137X urinary metabolite ratio (CMR) and plasma caffeine half life (T1/2). The CYP1A2 -3860A genotype was associated with a decreased risk of breast cancer. In contrast, distributions of the CYP1A2 -2467T/delT or -2467delT/delT and -163A/C or A/A genotypes among breast cancer patients and controls were similar. When the genotype and phenotype relationship was measured by comparing the mean CMR ratios and caffeine half life within the genotype groups between subjects and breast cancer patients, there were no significant differences except for -3860 A, most of them being homozygous for the -3860 G/G SNP and had a significant higher mean CMR ratio and half life than those with -3860 G/A (P=0.02). The results of this preliminary study show a significant association between CP1A2 -3860 G variant and CYP1A2 phenotype which must be confirmed by further large-size case-control studies.

• 한국생물공학회:학술대회논문집
• /
• 한국생물공학회 2005년도 생물공학의 동향(XVI)
• /
• pp.35-35
• /
• 2005

Recombinant human $interferon-{\beta}-1a(rIFN-{\beta})$ is a single glycosylated protein (at N80, 1N) with anti-viral activity. However, present drugs have a relatively short serum half-life of $rIFN-{\beta}$, thus patients suffer from frequent $infections.^{1)}$ To improve its half-life, eight glycosylation analogs were prepared, which have additional N-linked glycosylation consensus sequences (N-X-T/S) within the $IFN-{\beta}$ molecule and/or at C-terminal. Each $rIFN-{\beta}$ analog was examined for the presence of additional N-linked glycosylation and the maintenance of anti-viral activity in CHO cells. The molecular weights of five analogs were not changed. However, two analogs, R27T within $rIFN-{\beta}$ (27 kDa, 2N) and GNITVNITV at C-terminal (29kDa, 2N), showed a clear increase in molecular weights, compared to native $rIFN-{\beta}$ (23 kDa, 1N). And another combined analog of R27T+GNITVNITV showed increased molecular weight (33 kDa, 3N). It was confimed that the molecular weight increment of analogs was caued by the N-linked glycosylation with the treatment of N-glycansae. In the case of anti-viral activity, the analog GNITVNITV showed a reduction in activity compared to native $IFN-{\beta}$, whereas the analogs R27T and R27T+GNITVNITV were found to have distinctly increased activities. Pharmacokinetic study in rats also disclosed that the analogs R27T and R27T+GNITVNITV had 2 3 fold increased serum half-life, respectively. In conclusion, the addition of N-linked glycosylation in $rIFN-{\beta}$ increased serum half-life, thereby its less frequent administration will be expected.

• Archives of Pharmacal Research
• /
• 제27권6호
• /
• pp.662-669
• /
• 2004

The highly water-soluble monomethoxypoly(ethyleneglycol) (mPEG) prod rugs of cyciosporin A(CsA) were synthesized. These prod rugs were prepared by initially preparing intermediate in the form of carbonate at the 3'-positions of CsA with chloromethyl chloroformate, in the pres-ence of a base to provide a 3'-carbonated CsA intermediate. Reaction of the CsA intermediate with mPEG derivative in the presence of a base provides the desired water-soluble prod rugs. As a model, we chose molecular weight 5 kDa mPEG in the reaction with CsA to give water soluble prodrugs. To prove that the prod rug is decomposed in the body to produce CsA, the enzymatic hydrolysis test was conducted using human liver homogenate at $37^{\circ}C$. The prodrug was decomposed in human liver homogenate to produce the active material, CsA, and the hydrolysis half-life ($t_{1/2}$) of the prodrug, KI-306 was 2.2 minutes at $37^{\circ}C$. However, a demon-stration of non-enzymatic conversion in pH 7.4 phosphate buffer was provided by the fact that the half-life ($t_{1/2}$) is 21 hours at 37$^{\circ}C$. The hydrolysis test in rat whole blood was also conducted. The hydrolysis was seen with half-life ($t_{1/2}$) of about 9.9, 65.0, 14.2, 3.4, 2.1 9.5, and 1.6 minutes for KI-306, 309, 312, 313, 315, 316, and 317, respectively. This is the ideal for CsA prodrug. The pharmacokinetic study of the prodrug, KI-306, in comparison to the commer-cial product (Sandimmune Neoral Solution) was also carried out after single oral dose. Each rat received 7 mg／kg of CsA equivalent dose. Especially, the prodrug KI-306 exhibits higher AUC and $C_{max}$ than the conventional Neoral. The AUC and $C_{max}$ were increased nearly 1.5 fold. The kinetic value was also seen with $T_{max}$ of about 1.43 and 2.44 hours for KI-306 and Neoral, respectively.

• 한국정밀공학회지
• /
• 제17권1호
• /
• pp.145-152
• /
• 2000

X-ray diffraction method detects change of crystal lattice distance under material surface using diffraction angle 2$\theta$. This technique can be applied to the behavior on slip band and micro crack due to material degradation. The relation between half-value breadth and number of cycle has three stages which constitute rapid decrease in initial number of cycles, slight decrease in middle number of cycles and rapid decrease in final number of cycles. The ratio of half-value breadth takes a constant value on B/B$_{0}$-N diagram with loading condition except early part of fatigue life. The ratio of half-value breadth B/B$_{0}$ with respect to number of cycle to failure N$_{f}$ has linear behavior on B/B$_{0}$-log N$_{f}$ diagram. Therefore, in this paper the estimation of fatigue life by average gradient method has much less estimated mean error than the estimation of fatigue life by log B/B$_{0}$-log N/N$_{f}$ relation.elation.ation.

• 한국임상약학회지
• /
• 제1권1호
• /
• pp.31-36
• /
• 1991

Tobramycin is one of the most frequently selected agents for pharmacokinetic drug monitoring because of its narrow therapeutic index and essential role for the management of serious infections, especially gram-negative infections. Its pharmacokinetic parameters are dependent on race, sex, age, ideal body weight. disease states, and etc. Therefore, to schedule the dosing of tobramycin, the individual pharmacokinetic parameters such as half-life and volume of distribution are needed. However, these pharmacokinetic parameters have never been reported in Koreans. The purposes of this study were to evaluate the volume of distribution of tobramycin in cancer patients who had normal renal function, to compare the mean values of Vd reported in the literature, and to compare the measured half-life with the expected half-life based on ABW, LBW, and IBW, respectively. Venous blood samples were collected just before and thirty minutes after dosing during steady state. Serum tobramycin concentrations were determined by $TD_x$ (fluorescence immunoassay). IBW were measured by the method of Devine: and LBW were measured by the method of Hallynck. Creatinine clearances (CLcr) of the patients were estimated using the Cockcroft and Gault equation. Elimination rate constants (kel) were determined using the Welling and Craig equation. Infusion rate (ko), volume of distribution (Vd), and half-life $(t_{1/2})$ were determined using the Saw chuk and Zaske equation. The volume of distribution Was $27\%$ greater than the Schentag's study (0.26 vs 0.33 l/kg), but the half-life was similar to the Levy's study. The predicted half-lives based on IBW were the closest to actual half-lives (1.85 vs 2.01 hr).

• Journal of Applied Biological Chemistry
• /
• 제55권4호
• /
• pp.235-239
• /
• 2012

사과에 대한 diniconazole과 metconazole의 반감기와 잔류양상을 조사하였다. Diniconazole과 metconazole의 잔류허용기준은 둘 다 1.0 mg/kg으로서 0일차 기준량과 3회 처리구 모두 잔류 허용기준을 넘지 않았다. 재배기간 중 사과의 잔류농도는 약제살포 후 14일 경과 시 diniconazole은 기준량 및 3회 처리에서 0.01 및 0.02 mg/kg으로서 각각 88.9 및 93.8%의 농약이 분해되었다. Metconazole은 각각 0.04 및 0.11 mg/kg으로서 60.0 및 56.0% 정도의 농약 분해율을 보였다. Diniconazole의 사과중 반감기식은 기중량 처리구에서 y=$0.0811e^{-0.179x}$ ($r^2$=0.9693), 3회 처리구에서 y=$0.1451e^{-0.148x}$ ($r^2$=0.9677)이었으며 생물학적 반감기는 각각 3.9일 및 4.7일 이었다. Metconazole의 반감기식은 y=$0.0857e^{-0.055x}$ ($r^2$=0.9242) 및 y=$0.2304e^{-0.052x}$ ($r^2$=0.9544)이었고 생물학적인 반감기는 각각 12.6일 및 13.3일 이었다. Metconazole 기준량과 3회 처리의 경우 first order kinetic model 보다는 second order kinetic mode이 더 적합하였으며 반감기도 기준량에서 2일, 3회 처리에서 1일 감소되는 것을 알 수 있었다. 따라서 각 농약별로 잔류량과 시간과의 관계에 적합한 model을 찾아 반감기를 산출하는 것이 바람직 할 것으로 생각된다.

• 한국해양공학회지
• /
• 제7권2호
• /
• pp.103-113
• /
• 1993

X-ray diffraction analysis technique was used for the fatigue damage analysis and fatigue life prediction in Al 7075-T651 alloy. The tensile test, fatigue strength and fatigue crack propagation test with change of stress ratio were carried out. As a result, half-value breadth was increased with the plastic deformation in the specimen increasint at all test conditions. In particular, half-value breadth at the surface of the specimens fractured by fatigue was increased as stress intensity factor range and effective stress intensity factor range were increased. In addition, the good relationship between half-value breadty and diffraction pattern was shown.

• International Journal of Vascular Biomedical Engineering
• /
• 제1권2호
• /
• pp.13-19
• /
• 2003

Endothelial release of nitric oxide (NO) contributes to the regulation of vascular tone by inducing vascular relaxation. To estimate the blood flow-dependent nitric oxide level and half-life (T1/2) of nitric oxide in vivo state, we investigated the change of aortic NO currents during the change of aortic blood flow rate using NO-selective electrode system and electromagnetic flowmeter in the aorta of anesthetized rats. Resting mean aortic blood flow rate was $49.6{\pm}5.6ml/min$ in the anesthetized rats. NO currents in the aorta were increased by the elevation of blood pressure and/or blood flow rate. When the aortic blood flow was occluded by the clamping, aortic NO currents were decreased. The difference of NO concentration between resting state and occluded state was $1.34{\pm}0.26{\mu}M$ (n=7). This NO concentration was estimated as blood flow-dependent nitric oxide concentration in the rats. Also, while the aortic blood flow was occluded, NO currents were decreased with exponential pattern with $12.84{\pm}2.15$ seconds of time constant and $7.70{\pm}1.07$ seconds of half-life. To summarize, this study suggested that blood flow-dependent NO concentration and half-life of nitric oxide were about $1.3{\mu}M$ and 7.7 seconds, respectively, in the aorta of anesthetized rats. The nitric oxide-selective electrode system is useful for the direct and continuous measurement of NO in vivo state.

• Annals of Pediatric Endocrinology and Metabolism
• /
• 제22권1호
• /
• pp.15-26
• /
• 2017

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Patients with T2D suffer from various diabetes-related complications. Since there are many patients with T2D that cannot be controlled by previously developed drugs, it has been necessary to develop new drugs, one of which is a glucagon-like peptide-1 (GLP-1) based therapy. GLP-1 has been shown to ameliorate diabetes-related conditions by augmenting pancreatic ${\beta}-cell$ insulin secretion and having the low risk of causing hypoglycemia. Because of a very short half-life of GLP-1, many researches have been focused on the development of GLP-1 receptor (GLP-1R) agonists with long half-lives such as exenatide and dulaglutide. Now GLP-1R agonists have a variety of dosing-cycle forms to meet the needs of various patients. In this article, we review the physiological features of GLP-1, the effects of GLP-1 on T2D, the features of several GLP-1R agonists, and the therapeutic effect on T2D.

• 한국임상약학회지
• /
• 제8권2호
• /
• pp.89-94
• /
• 1998

Seasonal rhythmic changes in gentamicin pharmacokinetics was evaluated in 10 healthy male volunteers after single intravenous 80 mg administration of gentamicin at 9:00 a.m. during summer and winter. The mean terminal half-life and AUC of gentamicin were $3.56\pm0.14\;hr\;and\;25.03\pm2.84\;{\mu}g/ml{\cdot}hr$ in winter and $3.08\pm0.41\;hr\;and\;21.84\pm2.51\;{\mu}g/ml{\cdot}hr$ in summer. The mean total body clearance $(CL_t)$ and elimination rate constant $(k_{10})$ of gentamicin was $3.17\pm0.43\;L/hr,\;0.458\pm0.06\;hr^{-1}\;in\;winter\;and\;3.66\pm0.45\;L/hr,\;0.561\pm0.07\;hr^{-1}$ in summer, The mean volumn of distribution $(V_{dss})$ of gentamicin at steady state was $12.65\pm1.09$L in winter and $12.39\pm1.25$ L in summer. Serum concentrations of gentamicin in winter were increased significantly during 4-8 hr (p<0.05) compared to those of gentamicin in summer. The elimination rate constant $(k_{10})$ of gentamicin in winter was decreased significantly $(p<0.05)$ compared to that of gentamicin in summer. The mean volume of distribution at steady state $(V_{dss})$, AUC, mean total body clearance ($CL_t$) and terminal half-life of gentamicin in the winter were increased but were not significant. The mean intrasubject fluctuations in terminal half-life, AUC and $CL_t$ between winter and summer were 8.2, 11.0 and $6.0\%$ respectively.