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Translational and Clinical Pharmacology

  to  Present  ISSN: 2289-0882

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Volume of Distribution.

Nick HOLFORD ; Dong Seok YIM

Translational and Clinical Pharmacology.2016;24(2):74-77. doi:10.12793/tcp.2016.24.2.74

This tutorial deals with basic concepts of volume of distribution, the second most important parameter in pharmacokinetics but often challenging for students in clinical pharmacology. Its relationships with dose, concentration and amount in the body are discussed using a physical model and examples of commonly used drugs, as well as its physiological aspects pertaining to the physical volume of differing organs. Finally, application of volume of distribution to the calculation of loading dose and half-life is used to show how it is essential in pharmacotherapy and clinical pharmacology.
Drug Therapy ; Half-Life ; Humans ; Pharmacokinetics ; Pharmacology, Clinical

Drug Therapy ; Half-Life ; Humans ; Pharmacokinetics ; Pharmacology, Clinical

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Statistical basis for pharmacometrics: random variables and their distribution functions, expected values, and correlation coefficient.

Kyungmee CHOI

Translational and Clinical Pharmacology.2016;24(2):66-73. doi:10.12793/tcp.2016.24.2.66

For pharmacometricians, probability theory is the very first obstacle towards the statistics since it is solely founded on mathematics. The purpose of this tutorial is to provide a simple version of introduction to a univariate random variable, its mean, variance, and the correlation coefficient of two random variables using as simple mathematics as possible. The definitions and theorems in this tutorial appear in most of the statistics books in common. Most examples are small and free of subjects like coins, dice, and binary signals so that the readers can intuitively understand them.
Mathematics ; Numismatics ; Probability Theory

Mathematics ; Numismatics ; Probability Theory

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Problems within the post-marketing surveillance system in Korea: Time for a change.

Hyoyoung SONG ; Dong Seok YIM

Translational and Clinical Pharmacology.2016;24(2):63-65. doi:10.12793/tcp.2016.24.2.63

Post-marketing safety studies are an important tool for understanding and monitoring the safety profiles of drugs in the clinical setting. Their importance has attracted not only the attention of regulators for reinforcing legislation but also led to recent changes in European Union (EU) regulations; these regulations have influenced the practice of Post-Authorization Safety Study (PASS) by marketing authorization holders. Korea conducts post-marketing surveillance (PMS) studies, but their execution is very different. This editorial reviews the PMS system in Korea in comparison with the recent legislative changes affecting the EU system. Ultimately, it suggests that changes to the PMS system are necessary to obtain quality safety data while maintaining a global standard of operation. Such efforts to refine the system will enhance the credibility of the PMS in Korea and, in due course, produce safety profiles that will be valuable for public health.
European Union ; Korea* ; Marketing ; Public Health ; Social Control, Formal

European Union ; Korea* ; Marketing ; Public Health ; Social Control, Formal

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HPLC-UV method for the simultaneous determinations of ascorbic acid and dehydroascorbic acid in human plasma.

Yunjeong KIM ; Min Gul KIM

Translational and Clinical Pharmacology.2016;24(1):37-42. doi:10.12793/tcp.2016.24.1.37

A high performance liquid chromatography (HPLC) paired with UV-vis detection method to determine ascorbic acid and its oxidation product, dehydroascorbic acid, in human plasma was developed. Ascorbic acid in human plasma was extracted and stabilized using 10% metaphosphoric acid, and was analyzed by a Symmetry C18 column with 5 mM Hexadecyltrimethylammonium bromide and 50 mM KH2PO4 solution as the mobile phase (1.0 mL/min flow rate). Isoascorbic acid served as the internal standard and ultraviolet detector wavelength was 254 nm and 265 nm. Dehydroascorbic acid concentration was calculated from the differences in ascorbic acid concentration before and after reduction by dithiothreitol reagent. Quantification for ascorbic acid in human plasma was linear from 1–100 µg/mL. The inter- and intra-day precisions and accuracy were determined and the results were found to be within ±15%. This method was successfully applied to a human pharmacokinetic study of ascorbic acid as well as dehydroascorbic acid after oral administration of 4,000 mg vitamin C tablets to healthy Korean volunteers.
Administration, Oral ; Ascorbic Acid* ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Dehydroascorbic Acid* ; Dithiothreitol ; Humans* ; Plasma* ; Tablets ; Volunteers

Administration, Oral ; Ascorbic Acid* ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Dehydroascorbic Acid* ; Dithiothreitol ; Humans* ; Plasma* ; Tablets ; Volunteers

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Development and validation of a UPLC-MS/MS method for the quantification of acetaminophen in human plasma and its application to pharmacokinetic studies.

Jaemin CHA ; Bo Kyung KIM ; Mi Ri GWON ; Joomi LEE ; Boram OHK ; Woo Youl KANG ; Mi sun LIM ; Sook Jin SEONG ; Hyun Ju KIM ; Hae Won LEE ; Young Ran YOON

Translational and Clinical Pharmacology.2016;24(1):30-36. doi:10.12793/tcp.2016.24.1.30

We developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of acetaminophen concentration in human plasma. Following protein precipitated extraction, the analytes were separated and analyzed using an UPLC-MS/MS in the multiple reaction monitoring (MRM) mode with the respective [M+H]+ ions, m/z 152.06 → 110.16 for acetaminophen and m/z 180.18 → 138.12 for phenacetin (internal standard, IS). The method showed a linear response from 1 to 100 µg/mL (r > 0.9982). The limit of quantitation for acetaminophen in plasma was 1 µg/mL. The intra- and inter-day accuracy ranged in the ranges of 94.40–99.56% and 90.00–99.20%, respectively. The intra- and inter-day precision ranged in the ranges of 2.64–10.76% and 6.84–15.83%, respectively. This method was simple, reliable, precise and accurate and can be used to determine the concentration of acetaminophen in human plasma. Finally, this fully validated method was successfully applied to a pharmacokinetic study of acetaminophen in healthy volunteers following oral administration.
Acetaminophen* ; Administration, Oral ; Healthy Volunteers ; Humans* ; Ions ; Mass Spectrometry ; Phenacetin ; Plasma*

Acetaminophen* ; Administration, Oral ; Healthy Volunteers ; Humans* ; Ions ; Mass Spectrometry ; Phenacetin ; Plasma*

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Development of a validated liquid chromatography-tandem mass spectrometry assay for the quantification of simvastatin acid, the active metabolite of simvastatin, in human plasma.

Hyun Jung PARK ; Ae Kyung HWANG ; A Reum KIM ; Soo Hyeon KIM ; Eun Hwa KIM ; Sang Heon CHO ; Jong Lyul GHIM ; Sangmin CHOE ; Jin Ah JUNG ; Seok Joon JIN ; Kyun Seop BAE ; Hyeong Seok LIM

Translational and Clinical Pharmacology.2016;24(1):22-29. doi:10.12793/tcp.2016.24.1.22

Simvastatin is a lipid-lowering drug that is metabolized to its active metabolite simvastatin acid (SA). We developed and validated a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to quantitate SA in human plasma using a liquid-liquid extraction method with methanol. The protonated analytes generated in negative ion mode were monitored by multiple reaction monitoring. Using 500-mL plasma aliquots, SA was quantified in the range of 0.1-100 ng/mL. Calibration was performed by internal standardization with lovastatin acid, and regression curves were generated using a weighting factor of 1/χ2. The linearity, precision, and accuracy of this assay for each compound were validated using quality control samples consisting of mixtures of SA (0.1, 0.5, 5, and 50 ng/mL) and plasma. The intra-batch accuracy was 95.3-107.8%, precision was -2.2% to -3.7%, and linearity (r2) was over 0.998 in the standard calibration range. The chromatographic running time was 3.0 min. This method sensitively and reliably measured SA concentrations in human plasma and was successfully used in clinical pharmacokinetic studies of simvastatin in healthy Korean adult male volunteers.
Adult ; Calibration ; Humans* ; Liquid-Liquid Extraction ; Lovastatin ; Male ; Mass Spectrometry* ; Methanol ; Plasma* ; Protons ; Quality Control ; Running ; Simvastatin* ; Volunteers

Adult ; Calibration ; Humans* ; Liquid-Liquid Extraction ; Lovastatin ; Male ; Mass Spectrometry* ; Methanol ; Plasma* ; Protons ; Quality Control ; Running ; Simvastatin* ; Volunteers

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Brief introduction to current pharmacogenomics research tools.

Eun Young CHA ; Hye Eun JEONG ; Woo Young KIM ; Ho Jung SHIN ; Ho Sook KIM ; Jae Gook SHIN

Translational and Clinical Pharmacology.2016;24(1):13-21. doi:10.12793/tcp.2016.24.1.13

There is increasing interest in the application of personalized therapy to healthcare to increase the effectiveness of and reduce the adverse reactions to treatment. Pharmacogenomics is a core element in personalized therapy and pharmacogenomic research is a growing field. Understanding pharmacogenomic research tools enables better design, conduct, and analysis of pharmacogenomic studies, as well as interpretation of pharmacogenomic results. This review provides a general and brief introduction to pharmacogenomics research tools, including genotyping technology, web-based genome browsers, and software for haplotype analysis.
Delivery of Health Care ; Genome ; Haplotypes ; Humans ; Pharmacogenetics*

Delivery of Health Care ; Genome ; Haplotypes ; Humans ; Pharmacogenetics*

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Clinical pharmacologic aspects of immune checkpoint inhibitors in cancer therapy.

Kyu Pyo KIM ; Hun JUNG

Translational and Clinical Pharmacology.2016;24(1):7-12. doi:10.12793/tcp.2016.24.1.7

During the past two years, three immune checkpoint inhibitors, ipilimumab, nivolumab and pembrolizumab, have been approved and revolutionized cancer immunotherapy. Translational and clinical pharmacology of these agents have contributed in identifying patients who will receive benefit, dose effect relationship and surrogate endpoints of clinical benefit. In addition, population pharmacokinetics/pharmacodynamics have facilitated scientific clinical development, which has led to accelerated approval of these agents. This paradigm may show how early phase studies may allow identification of subgroup of patients who can benefit and subsequent approval of drugs based on smaller patient population. This may speed the access of effective treatment for patients with life-threatening diseases.
Biomarkers ; Humans ; Immunotherapy ; Pharmacokinetics ; Pharmacology, Clinical

Biomarkers ; Humans ; Immunotherapy ; Pharmacokinetics ; Pharmacology, Clinical

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How a VOICE for clinical pharmacology turns into a RECIPE for its development.

Jeffrey K ARONSON

Translational and Clinical Pharmacology.2016;24(1):1-6. doi:10.12793/tcp.2016.24.1.1

Pharmacology is the study of the actions of synthetic or semisynthetic chemicals or naturally occurring substances on molecules, cells, tissues, and living organisms, as seen in physiological and pathological systems, seeking to establish order, pattern, and sequence among them, aiming ultimately to determine the rules by which pathophysiological information can be coded into molecules, allowing prediction of both beneficial and harmful consequences. Clinical pharmacology is the application, informed by an understanding of pharmacology, of all aspects of the study and use of medicines in humans, whose practitioners, normally medically qualified, teach, do research, frame policy, and give information and advice about the actions and proper uses of medicines in humans and implement that knowledge in clinical practice. Clinical pharmacology expanded in the UK during the 1960s and 1970s and maintained a steady state during the 1980s, but thereafter started to decline. Since 2006 this decline has been halted and partly reversed through the efforts of the British Pharmacological Society, by demonstrating the need for clinical pharmacology in clinical practice, teaching, research, and policy making, and bringing that need to the attention of medical colleagues, regulators, government, and the public. Efforts continue to maintain and enhance this recovery, using the VOICE paradigm, which involves improving and maintaining the Visibility of the specialty, Outreach to advertise its attractiveness to potential trainees and creating a public image for the specialty, Integration with other disciplines, encouraging Coverage of neglected areas, and the use of Emissaries, particularly younger members of the discipline, to promote it, both within medicine and in the wider world. Fortuitously, translation of the five elements of this paradigm into Korean, and back-translation into English, with the addition of a sixth element, provides a RECIPE for the future of clinical pharmacology and therapeutics.
Humans ; Pharmacology ; Pharmacology, Clinical* ; Policy Making ; Voice*

Humans ; Pharmacology ; Pharmacology, Clinical* ; Policy Making ; Voice*

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A bioequivalence study of two levofloxacin tablets in healthy male subjects.

Inbum CHUNG ; Seonghae YOON ; Sojeong YI ; Bo Hyung KIM ; Sung Vin YIM ; In Jin JANG ; Howard LEE

Translational and Clinical Pharmacology.2014;22(2):102-105. doi:10.12793/tcp.2014.22.2.102

Levofloxacin is a bactericidal broad spectrum antibiotic against Gram-positive and Gram-negative pathogens. A randomized, two-treatment, two-period, two-way crossover study was conducted to evaluate the bioequivalence of Lectacin 250 mg tablet, a generic levofloxacin, to its reference drug, Cravit 250 mg tablet. Each period was separated by a 7-day washout. Serial blood samples were collected until 24 h after dosing and plasma levofloxacin concentrations were determined using a high performance liquid chromatography. Pharmacokinetic parameters were analyzed using K-BE Test 2007 and BA calc 2007 (Ministry of Food and Drug Safety, Cheongju-si, South Korea). The peak concentration (Cmax) and the area under the plasma concentration versus time curve from 0 to the last measurable concentration (AUC(0-t)) for the generic and reference levofloxacin were 4.48+/-0.89 mg/L and 4.46+/- 0.95 mg/L, and 25.33+/-4.12 mg*h/L and 25.77+/-4.01 mg*h/L, respectively, leading to a geometric mean ratio (90% confidence interval) of the generic to the reference levofloxacin of 1.0060 (0.9339-1.0842) and 0.9810 (0.9476-1.0159), respectively, for Cmax and AUC(0-t). Lectacin 250 mg tablet is bioequivalent to Cravit 250 mg tablet.
Chromatography, Liquid ; Chungcheongbuk-do ; Cross-Over Studies ; Humans ; Levofloxacin* ; Male ; Pharmacokinetics ; Plasma ; Tablets* ; Therapeutic Equivalency*

Chromatography, Liquid ; Chungcheongbuk-do ; Cross-Over Studies ; Humans ; Levofloxacin* ; Male ; Pharmacokinetics ; Plasma ; Tablets* ; Therapeutic Equivalency*

Country

Republic of Korea

Publisher

ElectronicLinks

Editor-in-chief

E-mail

Abbreviation

Translational and Clinical Pharmacology

Vernacular Journal Title

ISSN

2289-0882

EISSN

Year Approved

2011

Current Indexing Status

Currently Indexed

Start Year

Description

Previous Title

Journal of Korean Society for Clinical Pharmacology and Therapeutics

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