Jung Mi Oh

Seoul National University, Seoul, Seoul, South Korea

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Publications (49)137.32 Total impact

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    ABSTRACT: Individual differences in drug efficacy and toxicity remain an important clinical concern. We investigated copy number variation (CNV) frequencies for pharmacogenes using The Cancer Genome Atlas dataset.
    Pharmacogenetics and Genomics 11/2014; · 3.61 Impact Factor
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    ABSTRACT: Gene maturation differs between paediatric and adult populations and the extrapolation of adult pharmacogenomic information to paediatrics is not always appropriate. We sought to determine the extent of paediatric pharmacogenomic trial translation into US FDA-approved labels and to evaluate needs for biomarker studies. Using FDA's Table of Genomic Biomarkers and Drugs @ FDA website, 38 pharmacogenomic biomarkers in 56 drug labels were identified with possible application in paediatrics. Of these 56 drugs, biomarker comparison against “Very Important Pharmacogenes (VIPs)” defined in PharmGKB's database revealed a total of eight VIPs labelled among 41 drugs. 139 product reviews posted on the FDA website under the Best Pharmaceuticals for Children Act (BPCA) and Paediatric Research Equity Act (PREA) between October 2007 and July 2014 were examined. Review screening identified 43 drugs with “pharmacogenomic” content of which only three were true genotyping study reviews for proton pump inhibitors, all evaluating CYP2C19 polymorphisms. Pantoprazole was the sole drug labelled with pharmacogenomic information obtained specifically from paediatric trials. Clinicaltrials.gov was searched to further evaluate the current availability of pharmacogenomic studies in the paediatric population. Of the 33,132 trials registered on Clinicaltrials.gov, 137 were labelled as paediatric pharmacogenetic and pharmacogenomic studies. Pharmacogenomic studies directly conducted in paediatric patients are lacking and thus pharmacogenomic biomarker information based on adult studies is commonly presented in FDA-approved labels for use in paediatric patients. Considering differences in gene expression and physiological maturation between paediatric and adult populations, studies investigating pharmacogenomic effects specifically in paediatric patients should be conducted whenever significant biomarkers are available.This article is protected by copyright. All rights reserved.
    Basic & Clinical Pharmacology & Toxicology 10/2014; · 2.18 Impact Factor
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    ABSTRACT: Enteric-coated mycophenolate sodium (EC-MPS) is effective and safe in preventing rejection after transplantation and is mainly transported by ABCs and OATPs and metabolized by UGTs. The genetic polymorphisms affect the inter-individual variation in drug disposition and elimination. The aims of this study were to develop a population pharmacokinetic (PK) model and to evaluate the influence of genetic and clinical factors on the PK of mycophenolic acid (MPA) in Korean renal transplant recipients.
    European Journal of Clinical Pharmacology 08/2014; · 2.74 Impact Factor
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    ABSTRACT: Objectives Interleukin-10 (IL-10) is an important immunomodulatory cytokine. The association between IL-10 promoter gene polymorphisms and acute graft-versus-host disease (aGVHD) risk is established; however, results of these studies remain inconclusive. We performed a meta-analysis to clarify the effects of IL-10 promoter gene polymorphisms on aGVHD risk. Methods The authors searched MEDLINE, EMBASE, and Cochrane Library databases. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity. Results Finally, a total of 11 studies encompassing 3588 recipients and 3221 donors were included to study IL-10 -1082 G > A, -819 C > T, and -592 C > A polymorphisms. IL-10 -819 CC genotype was associated with an increased aGVHD risk (grade I-IV: OR, 2.722 (95% CI, 1.360-5.450); grade II-IV: OR, 2.265 (95% CI, 1.015-5.053)). Furthermore, patients who received grafts from donors with an IL-10 -819 CC genotype experienced more frequent grade I-IV aGVHD (OR, 2.306 (95% CI, 1.168-4.551)). Recipients with IL-10 -592 CC genotypes were at increased risk for grade II-IV aGVHD (OR, 1.999 (95% CI, 1.230-3.250)). Together, this meta-analysis found that IL-10 -819 CC and -592 CC polymorphisms increased aGVHD risk. Discussion and Conclusion This meta-analysis found the evidence that the IL-10 -819 CC and -592 CC genotypes in both recipients and donors increased the risk of aGVHD in allogeneic hematopoietic stem cell transplantation (HSCT) patients. These results contribute towards improving patient outcome through insight and rationale for individualized treatment strategies considering genetic determinants.
    Hematology (Amsterdam, Netherlands) 08/2014; · 1.33 Impact Factor
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    ABSTRACT: As tacrolimus has a rather narrow therapeutic range and high individual variability in its pharmacokinetics, it is important to determine the cause of the variation in tacrolimus pharmacokinetics. The purpose of this study was to establish a population pharmacokinetic-pharmacogenetic model of tacrolimus and identify co-variates that affect pharmacokinetic parameters to prevent fluctuations in the tacrolimus trough concentration during the early period after transplantation. Data from 1,501 trough concentrations and 417 densely collected concentrations were compiled from 122 patients who were on post-operative days 10-20 and analysed with a non-linear mixed-effect model. The first-order conditional estimation (FOCE) with interaction method was used to fit the model using the NONMEM program. Clinical/laboratory data were also collected for the same period, and CYP3A5 and ABCB1 genotypes were analysed for use in modelling from all included patients. An empirical Bayesian approach was used to estimate individual pharmacokinetic profiles. A one-compartment model with first absorption and elimination and lag time best described the data. The estimated population mean of clearance (CL/F), volume of distribution (V/F) and absorption rate (Ka ) was 21.9 L/h, 205 L, and 3.43 hr(-1) , respectively, and the lag time was fixed at 0.25 hr. Clearance increased with days after transplantation and decreased with CYP3A5*3/*3 about 18.4% compared to CYP3A5*1 carriers (P<0.001). A population pharmacokinetic model was developed for tacrolimus in early post-kidney transplantation recipients to identify co-variates that affect tacrolimus pharmacokinetics. Post-operative days and CYP3A5 genotype were confirmed as critical factors of tacrolimus pharmacokinetics. This article is protected by copyright. All rights reserved.
    Basic & Clinical Pharmacology & Toxicology 11/2013; · 2.18 Impact Factor
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    ABSTRACT: Individual differences in drug response can be caused by genetic and epigenetic variability and disease determinants. Pharmacoepigenetics is a new field that studies the expression changes in pharmacogenes without changes in DNA sequences. Epigenetic control mechanisms are associated with DNA methylation, histone modification, small noncoding RNAs, and nucleosome remodeling. Researchers are actively attempting to identify epigenetic mechanisms for controlling the expression of enzymes and transporters affecting the metabolism and disposition of drugs. Current evidence suggests that epigenetic changes play a major role in cytochrome P450 enzyme expression, major transporter function, and in interactions with nuclear receptors. A thorough understanding of pharmacoepigenetics provides insight into new approaches to drug discovery and development, provides an understanding of previously observed actions of older drugs, and provides a pathway by which epigenetics can be harnessed to provide better patient-specific therapy.
    Pharmacotherapy 10/2013; · 2.31 Impact Factor
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    ABSTRACT: Obesity is a chronic metabolic disease that affects an increasing number of people around the world. There have been limited studies evaluating the weight loss effects of orlistat in the Korean population, whose diet is different from that of the Caucasian population. The primary objective of this study was to evaluate the effect of orlistat on the weight and body mass index of obese and overweight Korean patients. The secondary objective was to evaluate the effects of orlistat on risk factors for obesity and metabolic disorders. Obese adult patients with a body mass index greater than 25 kg/m(2) who received 120 mg of orlistat three times daily for 24 weeks were included in this study. Patients were retrospectively evaluated for changes in body weight and body mass index, as well as waist and hip circumference, body fat levels, serum lipid levels, fasting glucose levels, and blood pressure. The evaluation included 63 patients. Treatment with orlistat for 4, 12, or 24 weeks significantly decreased the weight, body mass index, waist circumference, and hip circumference compared to that at the baseline. The average weight loss was 3.0 kg at 12 weeks and 3.6 kg at 24 weeks, which indicated a 3.8 and 4.6 % decrease from initial weight, respectively. The number of patients who lost more than 10 % of their initial body weight was 3 (4.8 %) at 12 weeks and 27 (7.9 %) at 24 weeks. About 27 % of patients reported gastrointestinal-related adverse effects with orlistat, but no serious adverse effects were reported. A retrospective study of overweight and obese Korean patients showed that treatment with orlistat for 24 weeks significantly decreased body weight and body mass index compared to the initial weight.
    Archives of Pharmacal Research 07/2013; · 1.54 Impact Factor
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    ABSTRACT: PURPOSE: To build a population pharmacokinetic (PK) model of cyclophosphamide (CY) and its metabolite, 4-hydroxycyclophosphamide (HCY), in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) and to identify covariates, including genetic polymorphisms, which affect CY and HCY PK parameters. METHOD: The study cohort comprised 21 patients undergoing HSCT who received CY intravenously between 2009 and 2011. Clinical characteristics and CY and HCY concentration data were collected for all patients, and ABCB1, ABCC2, GSTA1, GSTM1, GSTP1, GSTT1, CYP2B6, CYP2C19, and CYP3A5 genotyping was performed. A hypothetical enzyme compartment was conducted using the NONMEM program. RESULTS: A population PK analysis showed that the ABCC2 1249 genotype and aspartate aminotransferase levels significantly affected non-induced clearance (CL UI) and induced clearance (CL I) of CY, respectively. The final estimate of the mean CL UI and CL I of CY was 15.5 and 0.683 L/h, respectively, and the mean volume of distribution (V 1) of CY was 88.0 L. The inter-individual variability for CL UI, CL I, and V 1 of CY was 52.8, 200, and 18.0 %, respectively. Additionally, the CL UI of CY was significantly decreased to approximately 51 % in patients with the 1249 GA heterozygous genotype compared to those with the 1249 GG wild-type genotype (p < 0.05). There were only three heterozygous GA variants of ABCC2 1249 in the study patients. CONCLUSIONS: The population PK model developed in this study implies an influence of genetic factors on the clearance of CY. Clearance was moderately reduced in patients with the ABCC2 1249GA heterozygous genotype.
    European Journal of Clinical Pharmacology 04/2013; · 2.74 Impact Factor
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    ABSTRACT: BACKGROUND:The second-generation serotonin 5-HT(3) receptor antagonist palonosetron has shown improved efficacy in the prevention of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). However, there have been no randomized controlled trials supporting the preferential use of palonosetron in triple antiemetic regimens for patients receiving multiday highly emetogenic chemotherapy (HEC).OBJECTIVE:To compare the effectiveness of palonosetron-based and first-generation 5-HT(3) receptor antagonist-based triple antiemetic regimens in cancer patients receiving multiday HEC.METHODS:This was a review and analysis of medical record data. A total of 115 patients who had received multiday HEC were included and grouped into a palonosetron-based antiemetic group (n = 73) or a first-generation 5-HT(3) receptor antagonist-based antiemetic group (n = 42). Data on CINV were collected in 24-hour intervals for 120 hours after the start of chemotherapy.RESULTS:Complete response rates did not differ significantly between the 2 groups during any of the 3 phases: acute (0-24 hours), p = 0.877; overlap (24-120 hours), p = 0.997; and overall (0-120 hours), p = 0.723. The proportion of patients with complete control was similar between the groups during each phase: acute, p = 0.862; overlap, p = 0.838; and overall, p = 0.828. There was also no significant difference in other end points between the 2 groups. Among all patients, females experienced significantly more acute nausea (p = 0.040) and vomiting (p = 0.046) than males. Compared with nondrinkers, patients who consumed alcohol had a lower overall incidence of vomiting (p = 0.020).CONCLUSIONS:Within a triple antiemetic regimen, a palonosetron-based antiemetic regimen was not significantly different from regimens based on first-generation 5-HT(3) receptor antagonists in preventing CINV during multiday HEC.
    Annals of Pharmacotherapy 11/2012; · 2.92 Impact Factor
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    ABSTRACT: Oral mucositis (OM) is one of the most common and debilitating complications in patients undergoing intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for OM induced by intensive chemotherapy followed by HSCT. Patients were randomly assigned to either the rhEGF group or placebo group. The severity of OM and self-reported quality of life (QOL) were assessed daily. A total of 58 patients were analyzed. Baseline characteristics were similar between the two groups. The incidence of NCI grade ≥2 OM was higher in the rhEGF group (78.6% vs. 50%, P = 0.0496). However, the duration of OM in patients with NCI grade ≥2 tended to be shorter in the rhEGF group (8.5 days vs. 14.5 days, P = 0.262). The QOL analysis in patients with World Health Organization (WHO) grade ≥3 OM showed that rhEGF significantly reduced limitations in swallowing (P = 0.039) and drinking (P = 0.042). The duration of hospitalization (P = 0.047), administration of total parenteral nutrition (P = 0.012), and the usage of opioid analgesics (P = 0.018) were significantly shorter in the rhEGF group with WHO grade ≥3 OM. Adverse events were mild and similar between the two groups. In conclusion, this analysis showed that rhEGF did not reduce the incidence of NCI grade ≥2 OM. However, the patients with WHO grade ≥3 OM in the rhEGF group showed better results compared to the placebo group for several secondary endpoints. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
    American Journal of Hematology 11/2012; · 4.00 Impact Factor
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    ABSTRACT: BACKGROUND: For living donor liver transplantation, the genetic association of CYP3A5 genotype of recipient's native intestine and donor's liver allograft with tacrolimus pharmacokinetics has not been explained completely considering liver regeneration time. The goal of the study was to investigate the longitudinal effects of recipient-donor combinational CYP3A5 genotypes on tacrolimus dose-normalized concentration (C/D ratio) in blood. METHODS: Tacrolimus blood concentrations were measured for 58 Korean adult living donor liver transplant recipients on tacrolimus-based immunosuppressants during 4 years of follow-up. CYP3A5 was genotyped for both recipient and donor, and the recipient-donor combinational genetic effect on tacrolimus C/D ratios were evaluated as a function of time after adjusting for covariates including demographics and clinical variables. RESULTS: CYP3A5 expresser recipients grafted from CYP3A5 expresser donors consistently had the least C/D ratio throughout the entire study period, whereas CYP3A5 expresser recipients grafted from CYP3A5 nonexpresser donors had an intermediate, and CYP3A5 nonexpresser recipients grafted from CYP3A5 nonexpresser donors had the largest C/D ratio (all P < 0.01). The CYP3A5 nonexpresser recipients grafted from CYP3A5 expresser donors showed a significant decrease from the largest to the intermediate in C/D ratio for the first month. CONCLUSIONS: CYP3A5 genotypes of both recipient and donor were important factors influencing pharmacokinetic variability of tacrolimus. The recipient-donor combinational genetic effect on C/D ratio changed over time after transplantation.
    Transplantation 09/2012; 94(8):866-872. · 3.78 Impact Factor
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    ABSTRACT: For the past few decades, many statistical methods in genome-wide association studies (GWAS) have been developed to identify SNP-SNP interactions for case-control studies. However, there has been less work for prospective cohort studies, involving the survival time. Recently, Gui et al. (2011) proposed a novel method, called Surv-MDR, for detecting gene-gene interactions associated with survival time. Surv-MDR is an extension of the multifactor dimensionality reduction (MDR) method to the survival phenotype by using the log-rank test for defining a binary attribute. However, the Surv-MDR method has some drawbacks in the sense that it needs more intensive computations and does not allow for a covariate adjustment. In this article, we propose a new approach, called Cox-MDR, which is an extension of the generalized multifactor dimensionality reduction (GMDR) to the survival phenotype by using a martingale residual as a score to classify multi-level genotypes as high- and low-risk groups. The advantages of Cox-MDR over Surv-MDR are to allow for the effects of discrete and quantitative covariates in the frame of Cox regression model and to require less computation than Surv-MDR. Through simulation studies, we compared the power of Cox-MDR with those of Surv-MDR and Cox regression model for various heritability and minor allele frequency combinations without and with adjusting for covariate. We found that Cox-MDR and Cox regression model perform better than Surv-MDR for low minor allele frequency of 0.2, but Surv-MDR has high power for minor allele frequency of 0.4. However, when the effect of covariate is adjusted for, Cox-MDR and Cox regression model perform much better than Surv-MDR. We also compared the performance of Cox-MDR and Surv-MDR for a real data of leukemia patients to detect the gene-gene interactions with the survival time. leesy@sejong.ac.kr; tspark@snu.ac.kr.
    Bioinformatics 09/2012; 28(18):i582-i588. · 5.47 Impact Factor
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    ABSTRACT: Cytarabine arabinoside (ara-C) is the key agent for treating acute myeloid leukaemia (AML). Here, we genotyped 139 single nucleotide polymorphisms (SNPs) within the ara-C transport and metabolic pathway using the Illumina Golden Gate Assay in 97 patients with previously non-treated de novo AML other than M3. DCK rs4694362 (CC genotype) was a significant poor prognostic factor for overall survival (OS) (hazard ratio [HR], 33.202 [95% confidence interval (CI), 4.937-223.273], P<0.0001, P(Bonferroni)=0.017). SLC29A1 rs3734703 (AA or AC genotype) in combination with TYMS rs2612100 (AA genotype) was significantly associated with shorter relapse free survival (RFS) (HR, 17.630 [95% CI, 4.829-64.369], P<0.0001, P(Bonferroni)=0.021). These SNPs showed moderate or large interethnic divergence in allele frequencies from African or Caucasian populations. The results of our study suggest that a single SNP and SNP-SNP interactions may help to predict the drug response and provide a guide in developing individualised chemotherapy for AML patients receiving ara-C based chemotherapy.
    European journal of cancer (Oxford, England: 1990) 09/2012; · 4.12 Impact Factor
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    ABSTRACT: Cyclosporine is often used to prevent allograft rejection in renal transplant recipients. However, cyclosporine has a narrow therapeutic window and large variability in its pharmacokinetics. Individual characteristics and genetic polymorphisms can cause the variation. Hence, it is important to determine the cause(s) of the variation in cyclosporine pharmacokinetics. To our knowledge, this is the first reported population pharmacokinetic study of cyclosporine in living donor renal transplant recipients that considered the genetic polymorphism as a covariate. To build a population pharmacokinetic model of cyclosporine in living donor renal transplant recipients and identify covariates including CYP3A5*3, ABCB1 genetic polymorphisms that affect cyclosporine pharmacokinetic parameters. Clinical characteristics and cyclosporine concentration data for 69 patients who received cyclosporine-based immunosuppressive therapy after living donor renal transplantation were collected retrospectively for up to 400 postoperative days. CYP3A5 *1/*3 and ABCB1 C1236T, G2677T/A, C3435T geno-typing was performed. A population pharmacokinetic analysis was conducted using a NONMEM program. After building the final model, 1000 bootstrappings were performed to validate the final model. In total, 2034 blood samples were collected. A 1-compartment open model with first-order absorption and elimination was chosen to describe the pharmacokinetics of cyclosporine. A population pharmacokinetic analysis showed that postoperative days, sex, and CYP3A5 genotype significantly affected the pharmacokinetics of cyclosporine. The final estimate of mean clearance was 56 L/h, and the mean volume of distribution was 4650 L. The interindividual variability for these parameters was 22.98% and 51.48%, respectively. Using the present model to calculate the dose of cyclosporine with CYP3A5 genotyping can be possible for the patients whose cyclosporine concentration is not within the therapeutic range even with therapeutic drug monitoring.
    Annals of Pharmacotherapy 09/2012; 46(9):1141-51. · 2.92 Impact Factor
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    ABSTRACT: OBJECTIVE: We examined the differences in allele frequencies for pharmacogenes among the Korean (KOR), Chinese (CHB), Japanese (JPT), Caucasian (CEU), and Nigerian (YRI) populations. METHODS: Fifty-seven pharmacogenes were selected from the imputed Korean Association REsource and HapMap databases. Minor allele frequencies were analyzed using the sample size-modified single nucleotide polymorphism-specific fixation index (FST) and the χ-test with Bonferroni's correction. Geneset analysis was also carried out to identify pharmacogenes that have significantly different allele frequencies among the various populations tested. RESULTS: The KOR population was the most divergent group from the YRI population (FST: 0.079) but very similar to the CHB and JPT populations (FST: 0.003). VKORC1 showed a large population divergence in the KOR-YRI (0.439) comparison. CYP3A4 was also highly divergent in the KOR-YRI (FST: 0.361) comparison. The calcium signaling pathway gene set was divergent in all pairwise population comparisons. CONCLUSION: In terms of the 57 pharmacogenes studied, there were no significant differences among the KOR, CHB, and JPT populations. However, the YRI and CEU populations were significantly differentiated from the three Eastern Asian groups. Future pharmacogenomics studies can utilize the polymorphisms identified in this study, as these variants may have important implications for the selection of highly informative single nucleotide polymorphisms for future clinical trials.
    Pharmacogenetics and Genomics 09/2012; · 3.61 Impact Factor
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    ABSTRACT: Methotrexate (MTX) is often used to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, MTX has great pharmacokinetic variability and its use can result in fatal complications and/or infections after HSCT. The purposes of this study were to build a population pharmacokinetic model of MTX treatment in Korean patients who have undergone HSCT and to identify covariates, including genetic polymorphisms, that affect the pharmacokinetic properties of MTX. Clinical characteristics and MTX concentration data for 20 post-HSCT patients were collected. For each patient, ABCB1, ABCC2, ATIC, GGH, MTHFR, and TYMS genotyping was performed. Population pharmacokinetic analysis was performed using the NONMEM program. Analysis of MTX pharmacokinetic properties was accomplished using a 2-compartment pharmacokinetic model that incorporated first-order conditional estimation methods with interaction. The effects of a variety of demographic and genetic factors on MTX disposition were investigated. The study population consisted of 12 men (60%) and 8 women (40%). Median age and body weight were 28 years (range, 18-49 years) and 55.6 kg (range, 44.8-80.8 kg), respectively. Within the study population, the estimated mean MTX clearance (CL) was 7.08 L/h, whereas the mean central compartment volume (V(1)) of MTX distribution was 19.4 L. MTX CL was significantly affected by glomerular filtration rate (GFR), penicillin use, and the ABCB1 3435 genotype. Interindividual variabilities for CL and V(1) were 21.6% and 73.3%. A 10-mL/min GFR increase was associated with a 32% increase in mean MTX CL, whereas penicillin use was associated with a decrease in MTX CL of 61%. MTX CL was significantly greater (by ∼21%) in patients with the ABCB1 3435 CC and CT genotype than in those with the ABCB1 3435 TT genotype (P < 0.001). There was great interindividual variation in MTX pharmacokinetic properties in patients who had undergone HSCT. GFR, concurrent penicillin use, and the presence of the ABCB1 3435 C<T genotypes significantly affected MTX CL. The MTX population pharmacokinetic model developed here may provide useful information for individualizing MTX therapy after HSCT.
    Clinical Therapeutics 07/2012; 34(8):1816-26. · 2.23 Impact Factor
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    ABSTRACT: PURPOSE: Tacrolimus is a commonly used immunosuppressant in solid organ transplantation recipients, but it is characterized by a narrow therapeutic range and large inter-individual variability. The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of clinical covariates, including the genetic polymorphisms of the cytochrome P450 3A5 gene (CYP3A5) and gene encoding P-glycoprotein (ABCB1), on the PK parameters in adult Korean kidney transplant recipients. METHODS: Clinical data were collected retrospectively for 400 days after the initiation of a tacrolimus-based immunosuppression therapy. Data from 2,788 trough blood samples obtained from 80 subjects were used to perform a population PK analysis with a nonlinear mixed-effect model (NONMEM). RESULTS: The estimated population mean values of clearance (CL/F) and volume of distribution (V/F) were 22.9 L/h and 716 L, respectively, and the k ( a ) was fixed to 4.5 h(-1). The CYP3A5 genotype, hematocrit level, and post-operative days were identified as the main covariates that influence CL/F, and body weight was found to have a significant effect on V/F. Other covariates, including ABCB1 genotype, corticosteroid dosage, sex, and other clinical data, did not contribute to the pharmacokinetics of tacrolimus. CONCLUSIONS: This tacrolimus population PK model will be a valuable tool in developing rational guidelines and provides a basis for individualized therapy after kidney transplantation in clinical settings of Korea.
    European Journal of Clinical Pharmacology 06/2012; · 2.74 Impact Factor
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    ABSTRACT: Copy number variation (CNV) has been reported to be associated with chemotherapy response, which affects disease prognosis. Here, we determined the frequency of genome-wide cytogenetic CNV aberrations in Korean patients with normal karyotype (NK) acute myeloid leukaemia (AML) and tested whether these genomic variations contribute to differences in Ara-C and anthracycline-based chemotherapy responses. Bone marrow aspirates and blood from 30 previously untreated de novo NK-AML patients were provided at the time of diagnosis for copy number analysis. Possible associations between cytogenetic aberrations and clinical parameters were analysed. CNVs were identified in 23 (76.7%) of the 30 cases tested. Multivariate analyses controlled for other clinical co-variates showed that patients having copy number loss had a decreased probability of complete remission (OR, 0.015 [95% CI, 0-0.737], p = 0.035). Patients who had a copy number gain of more than four regions tended to have shorter event-free survival (EFS) (p = 0.083) with multivariate analysis showing that CNV increase is an independent predictive factor for shorter EFS (HR, 22.104 [95% CI, 1.644-297.157], p = 0.020). In addition, we identified candidate genes that may be involved in Ara-C and anthracycline drug response in Korean patients with NK-AML. These results suggest that CNVs may affect the success of Ara-C and anthracycline-based chemotherapy in Korean patients with NK-AML.
    Basic & Clinical Pharmacology & Toxicology 06/2012; 111(5):317-24. · 2.18 Impact Factor
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    ABSTRACT: The purpose of this study was to identify and characterize the association of various clinical variables and CYP3A5 genotypes with the pharmacokinetics of tacrolimus and outcome over 1-5 years in kidney transplantation patients in Korea. A total of 129 recipients (aged 18-65 years) administered tacrolimus were genotyped for CYP3A5 (6986A>G in intron 3; rs776746). Clinical covariates and trough levels, doses and dose-adjusted trough levels of tacrolimus, as well as complications during the 1-5 years after transplantation, were analysed. A linear mixed model was used to investigate potential factors affecting the trough levels, doses and dose-adjusted levels of tacrolimus. We identified factors affecting chronic allograft nephropathy (CAN) and tacrolimus-related complications. After adjusting for sex, body-weight and doses of corticosteroids and mycophenolate mofetil, we noted that CYP3A5 genotypes had the most profound effect on the dose and dose-adjusted trough levels of tacrolimus 1-5 years after transplantation (p < 0.001). Trough levels of tacrolimus were associated with post-transplantation hyperlipidaemia (p < 0.05), and estimated glomerular filtration rate was associated with CAN (p < 0.05). Therefore, the CYP3A5 genotype is a variable marker for tacrolimus dose requirement, and the trough level of tacrolimus should be controlled to minimize post-transplant hyperlipidaemia to achieve optimum outcome.
    Basic & Clinical Pharmacology & Toxicology 04/2012; 111(4):217-23. · 2.18 Impact Factor
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    ABSTRACT: The interleukin-6 (IL-6) -174 G>C genetic polymorphism has been implicated to play an important role in acute graft-versus-host disease (aGVHD). However, previous studies have yielded inconclusive results as to its role in patient susceptibility to aGVHD, and no study to date has systematically analyzed this polymorphism. A meta-analysis of the published evidence was conducted to estimate the true effect of the IL-6 -174 G>C genetic polymorphism in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients and donors on the risk of aGVHD. Seven cohort studies, comprising 1287 recipient and donor pairs, were included after eliminating 62 studies that met the following exclusion criteria: irrelevant studies other than cohort studies, without sufficient data, and with overlapping data. Although interstudy heterogeneity existed, most studies were conducted in the United States or Europe and included adult patients with hematologic disease who received alloHSCT from human leukocyte antigen-matched or identical sibling donors. The effect of the polymorphism on aGVHD risk (grades I-IV, II-IV, and III-IV) was estimated from odds ratios with 95% confidence intervals for the dominant genetic model and recessive model, respectively. Patients who received grafts from donors with the IL-6 G allele experienced more frequent grade I-IV aGVHD (odds ratio = 3.304 [95% confidence interval, 1.456-7.494]) and grade II-IV aGVHD (odds ratio = 1.738 [95% CI, 1.006 - 3.001]). To our knowledge, this is the first meta-analysis to evaluate the relation between a non-human leukocyte antigen gene polymorphism and the risk of aGVHD. Our meta-analysis combined the results of several studies and demonstrated that the donor IL-6 G allele is associated with an increased risk of grades I-IV and II-IV aGVHD.
    Clinical Therapeutics 02/2012; 34(2):295-304. · 2.23 Impact Factor

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1k Citations
137.32 Total Impact Points


  • 2003–2013
    • Seoul National University
      • • Research Institute of Pharmaceutical Sciences
      • • College of Pharmacy
      Seoul, Seoul, South Korea
  • 2002–2013
    • Sookmyung Women's University
      Sŏul, Seoul, South Korea
  • 2012
    • Soongsil University
      Sŏul, Seoul, South Korea
  • 2002–2008
    • Chungnam National University
      • Department of Physics
      Daiden, Daejeon, South Korea
  • 2007
    • Wooridul Spine Hospital Group
      Sŏul, Seoul, South Korea