• Title/Summary/Keyword: Clinical pharmacology

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The Safety and Pharmacokinetics of Cyanidin-3-Glucoside after 2-Week Administration of Black Bean Seed Coat Extract in Healthy Subjects

  • Jeon, Sang-Il;Han, Seung-Hoon;Lee, Jong-Tae;Hong, Tae-Gon;Yim, Dong-Seok
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.4
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    • pp.249-253
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    • 2012
  • We analyzed the pharmacokinetics of C3G on data from twelve subjects, after 2-week multiple dosing of black bean (Phaseolus vulgaris, Cheongjakong-3-ho) seed coat extract, using the mixed effect analysis method (NONMEM, Ver. 6.2), as well as the conventional non-compartmental method. We also examined the safety and tolerability. The PK analysis used plasma concentrations of the C3G on day 1 and 14. There was no observed accumulation of C3G after 2-week multiple dosing of black bean seed coat extract. The typical point estimates of PK were CL (clearance)=3,420 l/h, V (volume)=7,280 L, Ka (absorption constant)=9.94 $h^{-1}$, ALAG (lag time)=0.217 h. The black bean seed coat extract was well tolerated and there were no serious adverse events. In this study, we confirmed that a significant amount of C3G was absorbed in human after given the black bean seed coat extract.

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

  • Kang, Ju-Seop;Park, Yoo-Sin;Kim, Shin-Hee;Kim, Sang-Hyun;Jun, Min-Young
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.2
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    • pp.67-81
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    • 2011
  • Epilepsy is a chronic disease occurring in approximately 1.0% of the world's population. About 30% of the epileptic patients treated with availably antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, It has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and TDM in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring.

Role of miR-511 in the Regulation of OATP1B1 Expression by Free Fatty Acid

  • Peng, Jin Fu;Liu, Li;Guo, Cheng Xian;Liu, Shi Kun;Chen, Xiao Ping;Huang, Li Hua;Xiang, Hong;Huang, Zhi Jun;Yuan, Hong;Yang, Guo Ping
    • Biomolecules & Therapeutics
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    • v.23 no.5
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    • pp.400-406
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    • 2015
  • MicroRNAs (miRNAs) are a family of non-coding RNA that are able to adjust the expression of many proteins, including ATP-binding cassette transporter and organic cation transporter. We sought to evaluate the effect of miR-511 on the regulation of OATP1B1 expression by free fatty acids. When using free fatty acids to stimulate Chang liver cells, we found that the expression of miR-511 increased significantly while the expression of OATP1B1 decreased. We also proved that SLCO1B1 is the target gene of miR-511 with a bioinformatics analysis and using the dual luciferase reporter assay. Furthermore, the expressions of SLCO1B1 and OATP1B1 decreased if transfecting Chang liver cells with miR-511, but did not increase when transfecting the inhibitors of miR-511 into steatosis cells. Our study indicates that miR-511 may play an important role in the regulation of OATP1B1 expression by free fatty acids.

Survey on the undergraduate curriculum in clinical pharmacology and interns' prescribing ability in South Korea

  • Gu, Namyi;Kim, Kyong-Jee;Lim, Chi-Yeon;Lee, Jun Kyu;Rhee, Moo-Yong;Shin, Kwang-Hee;Lee, Seung-Hwan;Ahn, Sangzin
    • Translational and Clinical Pharmacology
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    • v.26 no.3
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    • pp.128-133
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    • 2018
  • Appropriate prescription writing is one of the critical medical processes affecting the quality of public health care. However, this is a complex task for newly qualified intern doctors because of its complex characteristics requiring sufficient knowledge of medications and principles of clinical pharmacology, skills of diagnosis and communication, and critical judgment. This study aims to gather data on the current status of undergraduate prescribing education in South Korea. Two surveys were administered in this study: survey A to 26 medical schools in South Korea to gather information on the status of undergraduate education in clinical pharmacology; and survey B to 244 intern doctors in large hospitals to gather their opinions regarding prescribing education and ability. In survey A, half of the responding institutions provided prescribing education via various formats of classes over two curriculums including lecture, applied practice, group discussions, computer-utilized training, and workshops. In survey B, we found that intern doctors have the least confidence when prescribing drugs for special patient populations, especially pregnant women. These intern doctors believed that a case-based practical training or group discussion class would be an effective approach to supplement their prescribing education concurrently or after the clerkship in medical schools or right before starting intern training with a core drug list. The results of the present study may help instructors in charge of prescribing education when communicating and cooperating with each other to improve undergraduate prescribing education and the quality of national medical care.

Effects of Leucocyanidins on TCDD-Induced Lipid Peroxidation in Female Rat (흰쥐에서의 2,3,7,8-Tetrachlorodibenzo-p-Dioxine 유발 지질 과산화 반응에 대한 Leucocyanidins(Vitis vinifera L.)의 효과)

  • Jhee Ok-Hwa;Lee Joo-Won;Kim Shin-Hee;Won Hei-Dan;Kim Hyun-Jin;Park Yun-Young;Kang Min-Jeong;Park Sung-Kug;Om Ae-Sun;Back Seung-Sam;Kang Ju-Seop
    • The Korean Journal of Food And Nutrition
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    • v.18 no.4
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    • pp.295-301
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    • 2005
  • Effects of leucocyanidins on the level of serum lipids and lipid peroxidation was investigated in 2,3,7,8-tetrachlorodibenzo-p-dioxine(TCDD)-induced rat that were pretreated with leucocyanidins for 4 weeks. The rats were divided into five experimental groups that is leucocyanidins and low TCDD treated group(LTL, 0.1 ${\mu}\;g/kg$ TCDD), leucocyanidins treated high TCDD group(LTH, 10 ${\mu}\;g/kg$ TCDD), No leucocyanidins and low TCDD treated group(NTL, 0.1 ${\mu}\;g/kg$ TCDD) and no leucocyanidins and high TCDD treated group(NTL, 10 ${\mu}\;g/kg$ TCDD). Serum total cholesterol, LDL-cholesterol and triglyceride level were significantly decreased and HDL-cholesterol level significantly increased in leucocyanidins treated group. Serum MDA level was also significantly reduced in leucocyanidins treated group. These results suggest that pre-supplement of leucocyanidins prevented the degree of lipid peroxidation on TCDD induced rat.

A Simple Dosing Scheme for Intravenous Busulfan Based on Retrospective Population Pharmacokinetic Analysis in Korean Patients

  • Choe, Sang-Min;Kim, Gayeong;Lim, Hyeong-Seok;Cho, Sang-Heon;Ghim, Jong-Lyul;Jung, Jin-Ah;Kim, Un-Jib;Noh, Gyu-Jeong;Bae, Kyun-Seop;Lee, Dong-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.4
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    • pp.273-279
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    • 2012
  • Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.

Cytochrome P450 2E1 Activity in a Korean Population

  • Muhn, Dou-Hyun;Chae, Ji-Min;Bahn, Jae-Yong;Song, Hae-Jung;Kim, Hyung-Kee;Kwon, Jun-Tack;Sohn, Dong-Ryul
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.5
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    • pp.597-602
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    • 1997
  • Cytochrome P450 2E1 (CYP2E1) is involved in the toxicity and carcinogenicity of a number of solvents and xenobiotics. Like the various types of oxidation pharmacogenetics, the activity of the enzyme shows a discernible interindividual and interethnic variation. However, no pharmacogenetic information on CYP2E1 polymorphism has been available from a Korean population. The aim of this study was to explore the pharmacogenetics of CYP2E1 polymorphism in a native Koreans after an oral 400 mg dose of chlorzoxazone administered to 128 subjects. Urine samples were collected during the subsequent 8-hour period and urinary concentrations of chlorzoxazone and 6-hydroxychlorzoxazone were determined by a high performance liquid chromatography with an ultraviolet detector. The limit of detection in the samples was found to be $0.5\;{\mu}g/ml$. The mean value of the 6-hydroxychlorzoxazone excreted in 8 hr urine expressed as the percentage was 48.2 13.8%. The frequency distribution of percentage of the administered dose excreted as the 6-hydroxy metabolite was unimodally distributed in the subjects studied. However, the values showed wide (7-fold) interindividual difference, ranged from 11.6% to 79.8% of the dose of chlorzoxazone. Thus, it was considered that the pharmacogenetic characteristics of CYP2E1 in a Korean population did not represent multimodal distribution in the 6-hydroxychlorzoxazone excreted in 8-hr urine expressed as the percentage. And the activity of the CYP2E1 in a Korean population seemed to be less compared with that of the Caucasian subjects.

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