http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Effects of Proton Pump Inhibitors on Metformin Pharmacokinetics and Pharmacodynamics
Kim, AnHye,Chung, Inbum,Yoon, Seo Hyun,Yu, Kyung-Sang,Lim, Kyoung Soo,Cho, Joo-Youn,Lee, Howard,Jang, In-Jin,Chung, Jae Yong American Society for Pharmacology and Experimental 2014 Drug metabolism and disposition: the biological fa Vol.42 No.7
<P>As inhibitors of organic cation transporters (OCTs), proton pump inhibitors (PPIs) may affect the plasma levels of metformin, an OCT substrate. We investigated the effects of two PPIs, pantoprazole and rabeprazole, on metformin pharmacokinetics and glucose levels in healthy subjects. In this open, randomized, six-sequence, three-period crossover study, 24 participants were administered metformin, either alone or in combination with pantoprazole or rabeprazole. The plasma concentrations of metformin and serum concentrations of glucose after a 75-g oral glucose tolerance test (OGTT) were determined. The area under the concentration-time curve (AUC) for metformin was 15% and 16% greater following coadministration with pantoprazole and rabeprazole, respectively. The maximum plasma metformin concentrations (<I>C</I><SUB>max</SUB>) also increased by 15% and 22%, respectively, compared with when it was administered without the PPIs. The percentage change in the AUC for glucose concentration versus time for metformin plus rabeprazole was significantly lower than that for metformin plus pantoprazole [geometric mean ratio: 0.96 (90% confidence interval: 0.92–0.99) and 0.77 (0.63–0.93), respectively]. There was no significant difference in the maximum glucose concentration. In conclusion, concomitant administration of PPIs with metformin significantly increased plasma metformin exposure, but the effects on glucose disposition were minor and varied depending on the PPI administered.</P>
Kim, Yun,Kim, Anhye,Lee, SeungHwan,Choi, Sung-Hak,Lee, Dae Young,Song, Ji-Su,Lee, Howard,Jang, In-Jin,Yu, Kyung-Sang Elsevier 2017 Clinical therapeutics Vol.39 No.9
<P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>Tedizolid phosphate is a next-generation oxazolidinone prodrug that is transformed into the active moiety tedizolid. Its indication is acute bacterial skin and skin structure infections caused by gram-positive species, including methicillin-resistant <I>Staphylococcus aureus</I>. Although tedizolid phosphate has been marketed in Korea, no data on the pharmacokinetic (PK) properties or tolerability of tedizolid phosphate in Korean subjects are available. This study was designed to evaluate the PK properties, oral bioavailability, and tolerability with a single-dose oral and intravenous administration of tedizolid phosphate in healthy Korean male subjects.</P> <P><B>Methods</B></P> <P>A block-randomized, double-blind, placebo-controlled, single-dose study was conducted in 3 groups (200, 400, and 600 mg; 10 subjects in each group). In the second part of the study, subjects from the 200-mg group received administration orally and intravenously (1-hour infusion) via 2-way crossover for the evaluation of absolute bioavailability. There was a 7-day washout period between treatments in the absolute bioavailability part of the study. Serial blood samples for PK analysis were collected for up to 72 hours. Tolerability was assessed by analysis of adverse events.</P> <P><B>Findings</B></P> <P>Thirty healthy Korean subjects completed the study and were included in the PK and tolerability analyses. Tedizolid phosphate was rapidly converted into tedizolid. After a single oral dose, the T<SUB>max</SUB> of tedizolid was observed to be 1.5 to 2.5 hours, and the plasma concentration–time curve of tedizolid showed a 2-phase elimination pattern, with a half-life of ~11 hours. Dose-dependent increases were observed in the AUC<SUB>last</SUB> value (29,441–78,062 μg · h/L) and in the C<SUB>max value (</SUB>2679–6980 μg/L) with the administration of tedizolid phosphate 200 to 600 mg PO. The absolute bioavailability of tedizolid was 95.2% (90% CI, 92.7%–97.8%) in the 200-mg administration group. There were no serious adverse events or clinically significant changes in the tolerability assessment.</P> <P><B>Implications</B></P> <P>Tedizolid phosphate at doses of up to 600 mg was well-tolerated in these healthy Korean male subjects. Tedizolid shows dose linearity with oral administration, and no dose adjustment of tedizolid phosphate 200 mg would be needed when switching administration routes. ClinicalTrials.gov identifier: NCT02097043.</P>
Kim, Yu Kyong,Kim, Anhye,Park, Shin Jung,Lee, Howard Dove Medical Press 2017 Drug design, development and therapy Vol.11 No.-
<P>To evaluate the pharmacokinetic (PK) and tolerability profiles of a new tablet formulation of tacrolimus and its interindividual variability (IIV) in the systemic exposure, and to compare them with those of the conventional capsule formulation, a randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in 47 healthy males. The capsule or tablet formulation of tacrolimus was orally administered, and serial blood samples were collected up to 96 hours after dosing. Whole-blood tacrolimus concentration was determined using liquid chromatography–tandem mass spectrometry. The maximum whole-blood tacrolimus concentration (C<SUB>max</SUB>) and the area under the whole-blood tacrolimus concentration–time curve from 0 hour to the last quantifiable concentration (AUC<SUB>last</SUB>) were compared between the two formulations. The similarity factor (f<SUB>2</SUB>) of the in vitro dissolution profiles was calculated. The geometric mean ratio (90% confidence interval) of tablet to capsule was 0.9680 (0.8873–1.0560) and 1.0322 (0.9359–1.1385) for C<SUB>max</SUB> and AUC<SUB>last</SUB>, respectively. The IIV of C<SUB>max</SUB> and AUC<SUB>last</SUB> of the tablet was smaller than the capsule. The f<SUB>2</SUB> values were >50 in all media. Both formulations were well tolerated. Thus, the tablet formulation of tacrolimus has smaller IIV in the systemic exposure than capsule, while having comparable PK and tolerability profiles, which may render it as a better treatment option for organ transplant patients.</P>
Chung, Hyewon,Kim, Anhye,Lim, Kyoung Soo,Park, Sang-In,Yu, Kyung-Sang,Yoon, Seo Hyun,Cho, Joo-Youn,Chung, Jae-Yong Lippincott, Williams and Wilkins 2017 International clinical psychopharmacology Vol.32 No.1
<P>Escitalopram is the (S)-enantiomer of citalopram that has a potential QT prolonging effect. In this study, 12 healthy elderly individuals received a single oral dose of escitalopram (20 mg), and their pharmacokinetics and QT effect data were compared with data from 33 younger adults obtained in a previous study. Serial blood samples for pharmacokinetic analysis were collected and ECG was performed up to 48 h postdose. The elderly and younger adults showed similar pharmacokinetic profiles. The geometric mean ratios (90% confidence interval) of the elderly compared with the younger adults were 1.02 (0.89-1.17) and 1.01 (0.86-1.17) for the maximum plasma concentration and area under the concentration-time curve, respectively. The mean baseline-adjusted QT (dQT) time profiles were similar and the mean values of maximum dQT were not significantly different between the elderly and the younger adults. The linear mixed-effect model indicated a weak but positive relationship between the escitalopram concentration and dQT, with an estimated coefficient of concentration of 0.43-0.54. In conclusion, the pharmacokinetics and QT effect of a single dose of escitalopram observed in the elderly without comorbidities and younger adults were generally similar. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.</P>
Oh, Jaeseong,Lee, SeungHwan,Kim, Anhye,Yoon, Jangsoo,Jang, Kyungho,Lee, Doo H.,Cho, Sunyoung,Lee, Sang Rim,Yu, Kyung-Sang,Chung, Jae-Yong Hall Associates, etc 2018 The Journal of Clinical Pharmacology Vol.58 No.1
<P>VVZ-149, a dual antagonist of GlyT2 and 5HT(2)A receptors, is an investigational analgesic with a novel mechanism of action that is currently under early-stage clinical development as an injectable agent for the treatment of postoperative pain. Here, the safety, tolerability, and pharmacokinetics of VVZ-149 injections in healthy male volunteers were explored in a randomized, double-blind, single- and multiple-ascending-dose (SAD and MAD, respectively), placebo-controlled clinical study. Subjects randomly received a 4-hour intravenous infusion of 0.25-8 mg/kg VVZ-149 or placebo in the SAD study (n = 46) or a 4-hour intravenous infusion of 4-7 mg/kg VVZ-149 or placebo twice daily for 3 days in the MAD study (n = 20). Serial blood and urine samples were collected for the pharmacokinetic analysis of VVZ-149 and its active metabolite (VVZ-368). Noncompartmental and compartmental pharmacokinetic analyses were performed. Various dosing scenarios were simulated to identify the adequate dosing regimen for the subsequent trials. Plasma exposure to VVZ-149 and VVZ-368 showed a dose-proportional increase. VVZ-149 did not accumulate in the plasma, whereas the plasma concentration of VVZ-368 increased by 1.23- to 2.49-fold after the fifth and sixth doses, respectively, in the MAD trial. Among the simulated dosing regimens, a loading dose followed by a maintenance dose was found to be an optimal dosing regimen, yielding the effective concentration estimated from animal studies in rat models of neuropathic or inflammatory pain. Single- or multiple-dose administration of VVZ-149 was generally well tolerated. These results showed that 0.5-8 mg/kg VVZ-149 exhibited linear pharmacokinetic characteristics and can be safely administered in further clinical studies.</P>
Choi Kihwan,Park Jong Eun,Kim Anhye,Hwang Sojung,Bae Jinkun,Shin Tae Gun,Kim Kyuseok 대한응급의학회 2022 Clinical and Experimental Emergency Medicine Vol.9 No.3
Objective Steroids are used in cases of sepsis, especially in patients experiencing septic shock. However, clinical trials to date have reported contradictory results. Different patient endotypes and variations in the type and dose of steroid may be at fault for this discrepancy, and further investigation is warranted. In this paper, we propose a new DEXA-SEPSIS study design. Methods We plan to conduct a multicenter, double-blinded randomized pilot study (DEXA-SEPSIS) investigating the feasibility and safety of early use of dexamethasone in sepsis. Participants will be high-risk septic patients presenting to the emergency department with a systolic blood pressure of <90 mmHg or serum lactate level of >2 mmol/L. Participants will be randomized to the following three groups: control, 0.1 mg/kg of dexamethasone, or 0.2 mg/kg of dexamethasone per day for 1 to 2 days. The primary outcome will be 28-day mortality. Secondary outcomes will include time to septic shock, shock reversal, additional steroid administration, number of ventilator-free days, use of continuous renal-replacement therapy, length of stay in the intensive care unit and/or hospital, delta Sequential Organ Failure Assessment score on days 3 and 7, superinfection, gastrointestinal bleeding, hypernatremia, and hyperglycemia. Discussion The DEXA-SEPSIS study will provide insight regarding the feasibility and safety of early use of dexamethasone in high-risk sepsis. The results could provide data to design a future phase III study.
Choi, Yewon,Lee, Sang Won,Kim, Anhye,Jang, Kyungho,Nam, Heesook,Cho, Young Lag,Yu, Kyung-Sang,Jang, In-Jin,Chung, Jae-Yong Oxford University Press 2018 The Journal of antimicrobial chemotherapy Vol.73 No.1
<P>Conclusions: LCB01-0371 is well tolerated in healthy male subjects with comparable haematology profiles to placebo, after multiple doses of up to 1200 mg twice daily for 21 days.</P>
Park, Sang-In,An, Hyungmi,Kim, Anhye,Jang, In-Jin,Yu, Kyung-Sang,Chung, Jae-Yong Informa UK (Taylor Francis) 2016 Expert opinion on drug safety Vol.15 No.8
<P>Background: This study evaluated the effects of atypical antipsychotic drugs and selective serotonin reuptake inhibitors (SSRIs) on the corrected QT (QTc) interval using a large database obtained from clinical settings. Additionally, the effects of factors including age on QTc intervals were estimated. Methods: Using an open-access QT database (ECG-ViEW), QTc-lengthening effects of 14 selected atypical antipsychotics and SSRIs were compared to those of a positive control drug, cilostazol, and a negative control drug, diazepam. We also evaluated effects of age, sexgender, and select electrolyte levels on observed QTc intervals. Results: The frequency of QTc prolongation with the pooled data of the 14 study drugs was lower than that with cilostazol (age-adjusted odds ratio (OR) = 0.43, 95% confidence interval (Cl) = 0.27-0.69), but no significant difference was found relative to when compared with that with diazepam (age-adjusted OR = 0.89, 95% Cl = 0.55-1.47). Furthermore, administration of the 14 study drugs significantly increased the QTc interval by 2.89 ms after each 10-year age increment (p-value < 0.0001). Conclusions: This study suggests that atypical antipsychotic drugs and SSRIs are less likely to be associated with QTc prolongation in clinical settings. In addition, age showed a significant association with the QTc interval. Further studies with well-characterized cohorts are warranted.</P>