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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The only existing study of CYP2D6*10-associated alterations in flecainide pharmacokinetics was retrospective. • Paroxetine has been known as a strong inhibitor of CYP2D6. WHAT THIS STUDY ADDS • This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians. AIMS The objectives were to evaluate the effect of CYP2D6 genetic polymorphism on the pharmacokinetics of flecainide, and also on the extent of drug interaction with paroxetine as a CYP2D6 inhibitor after a single oral administration in healthy subjects. METHODS An open-label, two-period, single-sequence, cross-over study was performed in 21 healthy Korean male volunteers (seven for CYP2D6*1/*1 or *1/*2, group 1; seven for CYP2D6*1/*10, group 2; seven for CYP2D6*10/*10 or *10/*36, group 3). Subjects were administered 200 mg of flecainide on day 1. After a 7-day wash-out period, subjects were administered 20 mg of paroxetine from day 8 to 14, and 200 mg of flecainide on day 15. Blood sampling was performed up to 72 h after flecainide administration. RESULTS Terminal elimination half-life and mean residence time (MRT) were significantly different among three genotype groups after a single oral administration of flecainide (P = 0.021, 0.011, respectively). Area under the concentration–time curve, terminal elimination half-life and MRT increased significantly after paroxetine co-administration only in groups 1 and 2. CONCLUSIONS This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians.

Objective The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene has been reported to be associated with the pharmacodynamics of antipsychotic drugs. We investigated the metabolic response of glucose in the brain to aripiprazole in relation to the DRD2 Taq1A polymorphism. Methods Twenty healthy male volunteers were recruited and were divided into two groups of 10 participants, according to their DRD2 genotypes (A1A1, n=10; A2A2, n=10). The volunteers received single oral doses of aripiprazole (10 mg) and a placebo, following a single-blind, placebo-controlled, randomized, two-way crossover study design. Brain glucose metabolism was assessed using positron emission tomography, scanned with 18F-fluorodeoxyglucose 12 h after the administration of the drug or placebo. Results In voxel-based analysis using SPM2, volunteers with the A2A2 genotype showed decreased metabolism in the right middle frontal gyrus, the left middle and inferior frontal gyrus, the right and left inferior temporal gyrus, and the right cingulate gyrus, and increased metabolism in the pons. In contrast, volunteers with the A1A1 genotype exhibited increased metabolism in the right caudate head, and no brain region showed decreased metabolism. In a region-of-interest analysis, significant interactions between drug and genotype were observed in the right medial orbitofrontal gyrus and the left caudate nucleus. Conclusions This suggests that DRD2 Taq1A polymorphism status may be associated with the clinical response to aripiprazole.

Pharmacokinetic and pharmacodynamic profiles of lorazepam and valproate were analyzed according to uridine 5'-diphosphate-glucuronosyltransferase (UGT)2B7 genotype in 14 healthy subjects with UGT2B15*2/*2 genotype. Systemic clearance of lorazepam (2 mg intravenously) and area under the concentration-time curve (AUC) of valproate (600 mg once daily for 4 days) were analyzed as pharmacokinetic parameters, and area under the effect-time curve (AUEC) of psychomotor coordination tests (Vienna) was used for pharmacodynamic parameter. No significant differences were found in systemic clearances of lorazepam by UGT2B7 genotype. AUCs of valproate showed an increasing tendency as the number of UGT2B7*2 alleles increased, but the difference was insignificant. Psychometric results were significant among the UGT2B7 genotype group (AUEC_tracking 261.5+/-298.9 in *1/*1, and 3,396.8+/-947 in *2/*2, P=0.047) when the two drugs were coadministered. Our study suggests that the UGT2B7 genotype probably affects lorazepam-valproate pharmacodynamic interaction, especially in subjects who have homovariant genotypes of UGT2B7 and UGT2B15, although the effects on the pharmacokinetics are less significant.

Multidrug resistance protein 2 (MRP2, ABCC2) plays an important role in the biliary clearance of a wide variety of endogenous and exogenous toxic compounds. Therefore, polymorphisms and mutations in the MRP2 gene may affect individual susceptibility to hepatotoxic reactions.Associations between genetic variations of MRP2 and toxic hepatitis were investigated using integrated population genetic analysis and functional molecular studies.Using a gene scanning method, 12 polymorphisms and mutations were found in the MRP2 gene in a Korean population. Individual variation at these sites was analyzed by conventional DNA screening in 110 control subjects and 94 patients with toxic hepatitis induced mostly by herbal remedies. When haplotypes were identified, over 85% of haploid genes belonged to the five most common haplotypes. Among these, a haplotype containing the g.-1774delG polymorphism showed a strong association with cholestatic or mixed-type hepatitis, and a haplotype containing the g.-1549GA, g.-24CT, c.334-49CT, and c.3972CT variations was associated with hepatocellular-type hepatitis. A comprehensive functional study of these sites revealed that genetic variations in the promoter of this gene are primarily responsible for the susceptibility to toxic liver injuries. The g.-1774delG variation and the combined variation of g.-1549GA and g.-24CT decreased MRP2 promoter activity by 36 and 39%, respectively. In addition, the promoter carrying the g.-1774delG allele showed a defect in the bile acid-induced induction of promoter activity.These results suggest that genetic variations of MRP2 are an important predisposing factor for herbal-induced or drug-induced toxic liver injuries.

Our objective was to investigate the effect of the uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B15 genetic polymorphism on the pharmacokinetics and pharmacodynamics of lorazepam in basal, inhibited, and induced metabolic states in healthy normal volunteers.Twenty-four healthy subjects were enrolled and grouped into UGT2B15*1/*1 or UGT2B15*2/*2 genotype groups. The pharmacokinetic and pharmacodynamic profiles of intravenous lorazepam were characterized before and after inhibition with 600 mg valproate once daily for 4 days and after induction with rifampin (INN, rifampicin) pretreatment (600 mg once daily for 10 days), with a washout period of 10 days between. The plasma concentrations of lorazepam and lorazepam glucuronide were analyzed before and at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours after lorazepam administration by liquid chromatography-tandem mass spectrometry. Visual analog scale assessments and psychomotor coordination tests were administered before and up to 12 hours after drug administration.The UGT2B15*2/*2 group showed 0.58-fold (95% confidence interval, 0.43-0.72; P.0001) lower systemic clearance during the basal state and 1.37-fold (95% confidence interval, 1.05-1.88; P = .037) higher area under the visual analog scale-time curve during the induced state compared with the UGT2B15*1/*1 group. The mean systemic clearance of lorazepam decreased by 20% in the inhibited state and increased by 140% in the induced state. During the inhibited or induced state, absolute values of clearance were consistently lower in the *2/*2 group, but the percent changes from baseline did not differ significantly by genotype.Our results suggest that the UGT2B15*2 polymorphism is a major determinant of interindividual variability with respect to the pharmacokinetics and pharmacodynamics of lorazepam.

Pitavastatin is a potent, newly developed 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor for the treatment of hyperlipidemia. We characterized the effects of organic anion transporting polypeptide 1 B 1 (OATP 1 B 1) alleles *1a, *1b, and *15 on the pharmacokinetics of pitavastatin.Twenty-four healthy Korean volunteers who had previously participated in a pharmacokinetic study of pitavastatin (single oral dose, 1--8 mg) were further investigated. Subjects were grouped according to OATP 1 B 1 genotype. Dose-normalized area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) values were analyzed, because different dosages were administered to subjects, whereas the pharmacokinetics showed linear characteristics.Dose-normalized pitavastatin AUCs for *1b/*1b (group 1), *1a/*1a or *1a/*1b (group 2), and *1a/*15 or *1b/*15 (group 3) were 38.8+/-13.3, 54.4 +/-12.4, and 68.1+/-6.3 ng.h.mL(-1).mg(-1) (mean+/-SD), respectively, with significant differences between all 3 groups (P=.008) and between subjects carrying and those not carrying the *15 allele (P = .004). Dose-normalized pitavastatin C(max) values were 13.2+/- 3.3, 18.2+/-5.7, and 29.4+/- 9.6 ng.mL(-1).mg(-1) in groups 1, 2, and 3, respectively, and also showed significant differences (P=.003) in a manner similar to that shown by AUC. No significant differences were found between the genotype groups in terms of dose-normalized AUC or C(max) values of pitavastatin lactone.OATP 1 B 1 variant haplotypes were found to have a significant effect on the pharmacokinetics of pitavastatin. These results suggest that the *15 allele is associated with decreased pitavastatin uptake from blood into hepatocytes and that OATP 1 B 1 genetic polymorphisms have no effect on the pharmacokinetics of pitavastatin lactone.

There have been considerable disagreements regarding the influence of MDR1 (ABCB1) polymorphisms on the disposition of P-glycoprotein (P-gp) substrates. We speculated that the unknown function of the A allele of exon 21 G2677T/A (Ala893Ser/Thr) provides one of the reasons for the contradictory results. This study was performed to clarify the effects of major MDR1 gene polymorphisms, including a variant A allele in exon 21, on fexofenadine pharmacokinetics.We investigated the occurrence of 3 high-frequency single-nucleotide polymorphisms (SNPs) in exons 12 (C1236T), 21 (G2677T/A), and 26 (C3435T) of the MDR1 gene in 232 healthy Koreans, using a polymerase chain reaction-restriction fragment length polymorphism method, and performed haplotype analysis on these 3 SNPs. A single oral dose of 180 mg fexofenadine hydrochloride was administered to 33 healthy Korean male volunteers, who were divided into 6 groups based on the MDR1 genotype for the G2677T/A polymorphism in exon 21 and the C3435T polymorphism in exon 26.A strong linkage disequilibrium was observed among the 3 SNPs. The frequencies of the 4 major haplotypes, 1236C-2677A-3435C, C-G-C, T-G-C, and T-T-T, were 16.4%, 18.6%, 21.6%, and 32.2%, respectively. Fexofenadine disposition varied considerably among the groups. In the 2677AA/3435CC genotype group (n=3), the values of area under the concentration-time curve from time 0 to 24 hours [AUC(0-24)] were significantly lower (P=.014) than those of the other 5 genotype groups (GG/CC, GT/CT, TT/TT, GA/CC, and TA/CT). As compared with the 2677GG/3435CC subjects, the AUC(0-24) values were 17% lower in the 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects (GG/CC versus AA/CC versus TT/TT, 4017 +/- 1137 ng . h/mL versus 3315 +/- 958 ng . h/mL versus 5934 +/- 2,064 ng . h/mL; P=.018). By stratification for genotypes at position 3435, homozygous 3435TT subjects were found to have significantly higher AUC(0-24) (P=.024) and maximum plasma concentration (P=.040) values than CC subjects [AUC(0-24), 5934 +/- 2064 ng . h/mL versus 3998 +/- 1241 ng . h/mL; maximum plasma concentration, 958 +/- 408 ng/mL versus 673 +/- 242 ng/mL].The plasma concentrations of fexofenadine after a single oral administration were lower in 2677AA/3435CC subjects than in subjects with the other 5 genotype combinations of the SNPs of G2677T/A and C3435T. These findings confirm the importance of analyzing MDR1 haplotypes and provide a plausible explanation for the conflicting results regarding the effect of MDR1 polymorphisms on the disposition of P-gp substrates.

Cytochrome P450 2B6 (CYP2B6) metabolizes a number of therapeutic drugs and its metabolic activity varies markedly in human liver. Although genetic polymorphisms of CYP2B6 have been reported in noncoding and coding regions, little information is available regarding single nucleotide polymorphisms (SNPs) and their haplotypes in noncoding regions in Asians. Fourteen previously reported SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism or SNaPshot analysis in a Korean population and their haplotypes were inferred from genotype data using an expectation-maximization algorithm. The most common haplotypes were haplotype I, the reference sequence (frequency 0.35), haplotype II (0.19), haplotype III (0.19), and haplotype V (0.12), which together accounted for 85% of all haplotypes. The frequency of haplotype III, which contains -2320C, -1778G, -1186G, -750C, and 15582T, was found to be 2.4-fold higher than that of the *1J allele in Caucasians, and the frequency of haplotype V, which contains -8207C, -1456C, -750C, 516T, and 785G, was 55% of that of the *6B allele in Caucasians. Moreover, haplotype V, the *6B allele, appeared to be completely linked to -8207 within a putative nuclear receptor binding motif, suggesting that lower expressions of the *6B allele may be associated with the presence of noncoding SNPs such as -8207G>C linked to nonsynonymous SNPs. In conclusion, we found 11 previously described polymorphisms and identified four major haplotypes of CYP2B6 in Koreans. The frequencies of the *1J or *6B alleles, which may reduce CYP2B6 enzyme expression, were found to be significantly different between Koreans and Caucasians.

Our objective was to investigate the effect of the CYP3A5 genotype on the systemic clearance of midazolam in constitutive, inhibited, and induced metabolic conditions.Nineteen healthy volunteers were grouped with regard to the CYP3A5*3 allele, into homozygous wild-type (CYP3A5*1/*1, n = 6), heterozygous (CYP3A5*1/*3, n = 6), and homozygous variant-type (CYP3A5*3/*3, n = 7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days) and also after rifampin (INN, rifampicin) pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between.The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the CYP3A5*3/*3 group showed a greater decrease in systemic clearance than was seen in the CYP3A5*1/*1 group (8.5 +/- 3.8 L. h(-1). 70 kg(-1) versus 13.5 +/- 2.7 L. h(-1). 70 kg(-1), P =.027). The 1'-hydroxymidazolam-to-midazolam area under the plasma concentration-time curve ratio was also significantly lower in the CYP3A5*3/*3 group (0.58 +/- 0.35 versus 1.09 +/- 0.37 for the homozygous wild-type group, P =.026).The CYP3A5 genotype did not affect the pharmacokinetics of intravenous midazolam in the basal or induced states. However, during cytochrome P450 (CYP) 3A inhibition by itraconazole, individuals carrying the CYP3A5*1 allele were found to be less susceptible to changes in systemic clearance and showed higher 1'-hydroxymidazolam-to-midazolam area under the plasma concentration-time curve ratios, probably resulting from the relatively CYP3A4-specific inhibition caused by itraconazole.

To evaluate the pharmacokinetic and pharmacodynamic characteristics of YH1885, a novel proton pump inhibitor, a single-blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 46 healthy volunteers. The volunteers were randomly allocated to single dose groups of 60 mg, 100 mg, 150 mg, 200 mg, and 300 mg (6 subjects per dose, including 2 placebos) or to multiple-dose groups of 150 mg and 300 mg (once-daily dosing for 7 days; 8 subjects per dose, including 2 placebos). The multiple-dose study was conducted separately after the single-dose study. YH1885 was administered orally after overnight fasting. Serial blood samples, urine samples, and pharmacodynamic measurements were taken. Drug concentrations in plasma and urine were determined by liquid chromatography/mass spectrometry (LC/MS). Pharmacodynamic changes were evaluated by ambulatory intragastric pH monitoring and by serial measurements of serum gastrin concentrations. Assessments of safety and tolerability also were made. Plasma concentrations of YH1885 reached peak levels 1.3 to 2.5 hours after single-dose administration and then declined monoexponentially with a terminal half-life (t(1/2)) of 2.2 to 2.4 hours in dosage groups up to 200 mg in the single-dose study. YH1885 showed linear pharmacokinetic characteristics, and little accumulation occurred after multiple administrations. The parent drug was not detected in urine. Dose-related pharmacological effects were obvious for dose groups of 150 mg and higher in the single-dose study. The mean intragastric pH and the percentage of time at pH>4 were significantly increased. The onset of drug effect was rapid, and maximal effects were observed on the first day of administration during multiple dosing. Serum gastrin levels also showed rapid increases during dosing but with a weak dose-effect relationship. Neither serious nor dose-limiting adverse effects were observed. YH1885 was found to be safe and well tolerated and effectively inhibited acid secretion with dose-dependent increases in intragastric pH. The acid-suppressing efficacy of YH1885 needs to be further evaluated in patients with gastric acid-related diseases.

A simple and sensitive high-performance liquid chromatographic with fluorescence detection method has been developed and validated for the determination of the new antitumor agent CKD-602 in human plasma. Plasma proteins were precipitated with methanol and the samples were acidified with 7% (v/v) perchloric acid. The supernatants were analyzed by HPLC using a Capcell Pak C 18 UG120 column and a mixture of methanol–0.1 M hexane-1-sulfonic acid in methanol–0.01 M TEMED in water at pH 6.0 (40:1:59, v/v) as the mobile phase. The lower limit of quantification was 0.2 ng/ml using 200 μl plasma samples. Mean within-run precision and between-run precision at six tested concentrations (0.2–400 ng/ml) were ≤10% and mean accuracy was ≤15%. Stability studies showed that CKD-602 is stable in both plasma and methanol extracts for at least 3 months at −30 °C. The described method was used for the pharmacokinetic analysis of CKD-602 during clinical phase I studies, in patients with solid tumors.

The pharmacokinetics of omeprazole and its metabolites in healthy subjects were evaluated to determine if a single dose of moclobemide inhibited CYP2C19 activity.Sixteen volunteers, of whom eight were extensive metabolizers (EM) and eight were poor metabolizers for CYP2C19, participated in two studies. Venous blood samples were collected for 24 h after oral ingestion of 40 mg omeprazole with or without 300 mg moclobemide coadministration. The pharmacokinetic change of omeprazole, omeprazole sulphone and 5-hydroxyomeprazole concentrations were assessed to test for an interaction between omeprazole and moclobemide.The coadministration of moclobemide in EMs approximately doubled the mean AUC (from 1834 to 3760 ng ml(-1) h) and C(max) (from 987 to 1649 ng ml(-1)) of omeprazole, and increased the AUC of omeprazole sulphone without changing AUC ratio of omeprazole to omeprazole sulphone. Moclobemide coadministration more than doubled the AUC ratio of omeprazole to 5-hydroxyomeprazole (from 2.5 to 5.3) in EMs, too. There was a significant decrease in Cmax and AUC of 5-hydroxyomeprazole in PMs but no significant changes were seen in the results for omeprazole and omeprazole sulphone AUCs.A single dose of moclobemide resulted in significant suppression of CYP2C19 activity in EMs. We conclude that physicians prescribing moclobemide should pay attention to its pharmacokinetic interactions even on the first day of coadministration with CYP2C19 substrates.

To evaluate the pharmacokinetic/pharmacodynamic characteristics of SKP-450, a novel K+ channel opener, a single blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 28 healthy volunteers. The volunteers were randomly allocated to dosage groups of 50 micrograms, 100 micrograms, 200 micrograms, and 300 micrograms. Single doses of SKP-450 were administered orally, after overnight fasting, and serial blood sampling and pharmacodynamic measurements were performed up to 48 hours after the drug was administered. The 200 micrograms group was further studied for food interactions in a crossover fashion. Drug concentrations in plasma were determined by HPLC. Hemodynamic changes after drug administration were evaluated by serial measurements of blood pressure (BP), pulse rate (PR), cardiac index (CI), and total peripheral resistance (TPR), using computerized impedance cardiography. Changes in plasma renin activity (PRA) and aldosterone concentrations (PAC) were determined 4 and 24 hours after drug administration. Both SKP-450 and SKP-818, an active metabolite, showed linear pharmacokinetic characteristics, and food intake did not significantly affect the pharmacokinetic characteristics of either compound. Dose-related pharmacological effects were obvious for both the 200 micrograms and 300 micrograms groups. Hemodynamic parameters related to vasodilation and reflex tachycardia, such as maximum changes in diastolic BP, PR, CI, and TPR, showed significant dose-dependent changes. The area under the time-effect curve (AUEC) of the parameters also showed a similar dose-dependent pattern. The PRA and PAC exhibited significant changes 4 hours after drug administration in the 300 micrograms group. Adverse effects, such as headaches, were more frequently observed at the higher dose levels. SKP-450 was generally well tolerated by these normotensive subjects. The antihypertensive efficacy of SKP-450 needs to be evaluated in hypertensive patients after multiple dosing.

Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods: A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results: A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were generally well tolerated. Conclusion: At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability. Keywords: itopride, extended-release, immediate-release, bioavailability, pharmacokinetics

일반적으로 혈청에는 세포가 포함되어 있지 않고 이에 따라 DNA가 존재하지 않는다고 알려져 있지만, DNA typing과 분 석이 가능함을 몇몇 논문에서 제기해 왔다. 혈액 응고 과정 중 남아있는 세포 조각(debris)들이 유전자 분석을 하기에 충분 한 양을 제공해 준다는 것이다. 그러나 아직 혈청에서 DNA typing이 얼마나 가능한지에 대해서는 자료들이 충분하지 않 다. 진단 검사와 면역 등 다양한 분야에서 혈청을 대상으로 연구 를 하고 있다. 이러한 연구 중 시료가 바뀌었다고 의심을 가지 게 되는 경우나 혈청이 누구의 것인지 다시 한번 확인하는 것 이 필요한 상황에서는 혈청만이 시료를 확인하는 유일한 대상 일 수 있다. 지금까지 혈청은 DNA가 존재 하지 않거나, 매우 적다는 이유로 DNA typing 또는 분석을 하지 않았다. 하지만 혈청에 존재하는 소량의 DNA로도 친자 확인이나 개인 식별을 위한 유전자 검사가 가능하다면 혈청도 법의학적 DNA source 중 하나가 될 수 있을 것이다. 본 연구에서는 혈청의 유전자를 이용한 개인식별을 진행하 여 효과적으로 혈청들을 구분하였다. 이런 과정에서 일상적인 유전자 검사가 가능할 정도로 혈청에서도 DNA를 추출할 수 있었고, 상용화된 PCR(polymerase chain reaction) kit를 사용 해 유전자 분석을 시행할 수 있었다. 이를 증례의 형태로 보고

=Abstract= Pharmacokinetics, Pharmacodynamics and Safety of JES9501 after Single and Multiple Oral Administration in Healthy Subjects AnHye Kim, Bo-Hyung Kim, Dongseong Shin, Joo-Youn Cho, Kyung-Sang Yu, In-Jin Jang, Jae-Yong Chung Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea, Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital, Seoul, Republic of Korea , Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea

Subjectively small or absent stomach bubble on classical ultrasound scan is associated with tracheoesophageal fistula/esophageal atresia and appropriate diagnosis of esophageal atresia (EA) significantly improve outcome. The antenatal diagnosis of esophageal atresia by the presence of polyhydroamniosis and an absent stomach bubble is well documented. A significant number of esophageal atresia are associated with a tracheoesophageal fistula. We present a case of long gap esophageal atresia with a fistula diagnosed prenatally by 3D US at 32 weeks 5days (Accuvix, Medison, korea). The 3D US findings are an absent stomach, polyhydroamnios, pouch sign of the esophageal blind end. After delivery, the baby had twice operations for long gap esophageal atresia with tracheoesophageal fistula (on the 11th day: tracheoesophageal fistula ligation with gastrostomy, on the 2 months later: intrathoracic esophagogastrostomy). Technique of reconstructing 3D volume is fast, accurate and produces high-quality images that are easy to reproduce of tracheal pouch.