• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.155-164
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• 2006

Great inter-variability in drug response and adverse drug reactions is related to inter-variability of drug bioavailability, drug interaction and patient's disease and physyological state that cause change in absorption, distribution, metabolism and excretion of drugs. However, these alone do not sufficiently predict and explain inter-variability in drug response. In recent studies, it is reported that inter-variability in drug response and adverse drug reactions may largely resulted from genetically determined differences in drug absoption, distribution, metabolism and drug target proteins. Especially, the major human drug-metabolizing enzymes such as CYP450, N-acetyl tranferase, thiopurine S-methyl transferase, glutathione S-transferase are identified as the major gene variants that cause inter-individual variability in drug's response and adverse drug reactions. These variations may have most significant implications for those drugs that have narrow therapeutic index and serious adverse drug reactions. Therefore, the genetic variation such as polymorphisms in drug metabolizing enzymes can affect the response of individuals to drugs that are used in the treatment of depression, psychosis, cancer, cardiovascular disorders, ulcer and gastrointestinal disorders, pain and epilepsy, among others. This review describes the pharmacogenomics of the drug metabolizing enzymes associated with the drug response and its clinical applications.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.476-480
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• 2005

Immunosuppressive therapy in pediatric renal transplant recipients is changing consequence of the increasing number of available immunosuppressive agents. The optimal use of immunosuppressive agents requires a thorough understanding of the pharmacokinetic characteristics, but the information on the pharmacokinetic characteristics of these drugs in pediatric transplant recipients is still limited. In general, patients younger than 5 years old show higher clearance rates, therefore the need for higher dosages in younger patients seems evident. By the therapeutic drug monitoring, trough($C_{min}$) and peak level($C_{max}$) are measured and the area under the blood concentration-time curve(AUC), which is taken as being representative of total systemic exposure can be calculated. Cyclosporine A (CSA) has poor bioavailability, which contributes to high inter- and intra-patient pharmacokinetic variability. CSA concentration measured 2 hours after administration($C_2$) has better correlation with the AUC than $C_{min}$ and is an alternative technique that predicts the AUC. Tacrolimus(Tac) has a great deal of inter-individual variability like CSA but intra-individual variability in systemic exposure is considered to be low. Both CSA and Tac are metabolized by a cytochrome P-450 enzyme isoform(CYP3A4). We should consider changing the dosages when CSA or Tac is used in combination with the medicines that inhibit or induce the CYP3A4. In case of steroid-free immunosuppressive therapy, the blood concentration of Tac should be frequently checked and dosage adjustment may be needed.

• BMB Reports
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• v.36 no.1
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• pp.1-11
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• 2003

The causative role of polycyclic aromatic hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention of chemoprevention studies. The successful applicability of DNA adducts as early endpoints depends on several criteria:i.adduct levels in easily accessible surrogate tissues should reflect adduct levels in target-tissues, ii. toxicokinetics and the temporal relevance should be properly defined.iii. sources of inter- and intra-individual variability must be known and controllable, and finally iv. adduct analyses must have advantages as compared to other markers of PAH-exposure. In general, higher DNA adduct levels or a higher proportion of subjects with detectable DNA adduct levels were found in exposed individuals as compared with non-exposed subjects, but saturation may occur at high exposures. Furthermore, DNA adduct levels varied according to changes in exposure, for example smoking cessation resulted in lower DNA adduct levels and adduct levels paralleled seasonal variations of air-pollution. Intra-individual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Inter-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH-metabolism and deserves further investigation. DNA adduct measurement may have three advantages over traditional exposure assessment: i. they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over a longer period of time. Therefore, DNA adduct assessment may reduce the monitoring effort. ii. Biological monitoring of DNA adducts accounts for all exposure routes. iii. DNA adducts may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. In conclusion, there is now a sufficiently large scientific basis to justify the application of DNA adduct measurement as biomarkers in exposure assessment and intervention studies. Their use in risk-assessment, however, requires further investigation.

• Phonetics and Speech Sciences
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• v.9 no.3
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• pp.25-32
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• 2017

Besides their effect on the f0 contour of the following vowel, Korean stops are undergoing a sound change in which a partial or complete consonantal merger on voice onset time (VOT) is taking place between aspirated and lax stops. Many previous studies on sound change have mainly focused on group-normative effects, that is, effects that are representative of the population as a whole. Few systematic quantitative studies of change in adult individuals have been carried out. The current study examines whether the sound change holds for individual speakers. It focuses on inter-speaker and intra-speaker variability on sound change in contemporary Korean. Speech data were collected for thirteen Seoul Korean speakers studying abroad in America. In order to minimize the possible effects of speech production, socio-phonetic factors such as age, gender, dialect, speech rate, and L2 exposure period were controlled when recruiting participants. The results showed that, for nine out of thirteen speakers, the consonantal merger is taking place between the aspirated and lax stop in terms of VOT. There were also intra-speaker variations on the merger in three aspects: First, is the consonantal (VOT) merger between the two stops is in progress or not? Second, are VOTs for aspirated stops getting shorter or not (i.e., the aspirated-shortening process)? Third, are VOTs for lax stops getting longer or not (i.e., the lax-lengthening process)? The results of remarkable inter-speaker and intra-speaker variability indicate a synchronous speech sound change of the stop system in contemporary Korean. Some speakers are early adopters or active propagators of sound change whereas others are not. Further study is necessary to see whether the inter-speaker differences exceed intra-speaker differences in sound change.

• International Journal of Industrial Entomology and Biomaterials
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• v.8 no.2
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• pp.211-215
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• 2004

Genetic diversity within the natural populations of Daba ecorace of Antheraea mylitta Drury was studied using individual silkworms collected from the South Singhbhum district of Jharkhand state of India with 21 inter simple sequence repeat (ISSR) primers. A total of 148 bands were produced, of which 79% was polymorphic. The pair wise genetic distance among the individuals varied from 0.186 to 0.329. The dendrogram grouped the individuals into 3 major clusters. Nei's heterozygosity analysis revealed 0.265 ${\times}$ 0.18 variability within the population. The high genetic variability present within the natural population of Daba ecorace of A. mylitta is indicative of their adaptational strategy in nature and have much importance for in situ conservation as well as utilization in breeding programs.

• Korean Journal of Clinical Pharmacy
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• v.27 no.2
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• pp.63-68
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• 2017

Neonates have large inter-individual variability in pharmacokinetic parameters of many drugs due to developmental differences. The aim of this study was to investigate the factors affecting the pharmacokinetic parameters of drugs, which are commonly used in critically ill neonates. Factors that reflect physiologic maturation such as gestational age, postnatal age, postconceptional age, birth weight, and current body weight were correlated with pharmacokinetic parameters in neonates, especially preterm infants. Comorbidity characteristics affecting pharmacokinetics in critically ill neonates were perinatal asphyxia, hypoxic ischemic encephalopathy, patent ductus arteriosus (PDA), and renal dysfunction. Administration of indomethacin or ibuprofen in neonates with PDA was associated with the reduced clearance of renally excreted drugs such as vancomycin and amikacin. Therapeutic hypothermia and extracoporeal membrane oxygenation were influencing factors on pharmacokinetic parameters in critically ill neonates. Dosing adjustment and careful monitoring according to the factors affecting pharmacokinetic variability is required for safe and effective pharmacotherapy in neonatal intensive care unit.

• International Journal of Contents
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• v.16 no.1
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• pp.25-33
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• 2020

We develop a simulation method that affords very high variability of virtual pedagogical situations involving many independent plans, still achieves authoring (or implementation) scalability. While each individual plan would be coherently drawn up by an agent for its respective goal, those independently-made plans might be coincidentally intertwined in their execution. The inevitable non-determinism involved in this multi-event plan encompassing pre-planned and unforeseen events is resolved by (multi-phase) dynamic planning and articulated sequencing of events in contrast to static planning and monolithic authoring in conventional narrative systems. Connections between events are dictated by their associated rules and their actual connections are dynamically determined in execution time by current conditions of background-world. This unified connection scheme across pre-planned and unforeseen events allows a multi-plan, multi-agent situation to be coherently planned and executed in a global scale. To further the variability of a situation, the inter-event coupling is made in a fine level of action along with a limited episteme of each agent involved. We confirm analytically the viability of our approach with respect to the situation variability and authoring scalability, and demonstrate its practicality with an implementation of a composite situation.

• Human Ecology Research
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• v.56 no.2
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• pp.157-165
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• 2018

Using data from the Panel Study on Korean Children, this study investigated whether children with high levels of problem behaviors adjusted more poorly on the $1^{st}-grade$ than children with low levels of problem behaviors, and whether there was evidence of intra-individual stability in behavior problems over time. Data were analyzed by use of the Latent Growth Model and group differences analyses. Three findings were noteworthy. First, there was evidence of intra-individual and inter-individual variability in behavior problems between poor- and non-poor household children. Second, children with higher initial levels of internalizing and externalizing behaviors at 4 years had lower school readiness scores at 6 years. Finally, children with lower levels of school readiness at 6 years had lower school adjustment scores in $1^{st}$ grade. The results discuss implications for future research and policies for preschool children. With mediating effect of school readiness, developmental trajectories of child's problem behavior have been found to be predictors of delayed achievements in school. The results show that intervention programs are necessary for children with high levels of problem behavior. This study also showed that children who experienced poverty at home could have more difficulties in school readiness and school adjustment.

• PNF and Movement
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• v.15 no.3
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• pp.361-371
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• 2017

Purpose: The purpose of this study was to examine the effects of performing a dual task on gait velocity, temporospatial variables, and symmetry in subjects with subacute stroke. Methods: The study included 14 independent community ambulators with gait velocity of 0.8m/s. The Korean mini-mental state examination, the Berg balance scale, the Trunk impairment scale, and the Fugl-Meyer assessment scale were used to recruit homogeneous subjects. Subjects performed a single task (10m ambulation at a comfortable speed) and a dual task (10m ambulation at a comfortable speed while carrying a water-filled glass). Gait variables were examined with the OptoGait system. Results: The findings of this study were as follows: 1) Gait velocity decreased significantly in the dual-task condition as compared to the single task condition. 2) There were no significant differences between the paretic and non-paretic stances. 3) Paretic swing decreased significantly in the dual-task condition as compared to the single task condition. 4) The non-paretic, double-limb support phase increased significantly in the dual-task condition as compared to the single- task condition. 5) There was no significant difference in temporal symmetry. 6) Non-paretic step length decreased significantly in the dual-task condition as compared to the single-task condition. 7) There was no significant difference in spatial symmetry. Conclusion: Performing dual tasks decreases gait velocity, paretic swing phase, and non-paretic step length, while it increases non-paretic double limb support. In addition, although there is no difference in temporospatial symmetry, there is high inter-subject variability in temporospatial symmetry. Thus, dual tasks should be selected in accordance with the functional level of the hemiplegic patient, and inter-subject variability of the individual should be considered when dual tasks are considered for gait-training of hemiplegic patients.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.11a
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• pp.51-66
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.