Translational and Clinical Pharmacology最新文献_第7页

Determination of candesartan or olmesartan in hypertensive patient plasma using UPLC-MS/MS. UPLC-MS/MS法测定高血压患者血浆中坎地沙坦或奥美沙坦的含量。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-12-01 Epub Date: 2021-12-16 DOI: 10.12793/tcp.2021.29.e21

Hyeon-Cheol Jeong, Yo-Han Seo, Namyi Gu, Moo Yong Rhee, Kwang-Hee Shin

{"title":"Determination of candesartan or olmesartan in hypertensive patient plasma using UPLC-MS/MS.","authors":"Hyeon-Cheol Jeong, Yo-Han Seo, Namyi Gu, Moo Yong Rhee, Kwang-Hee Shin","doi":"10.12793/tcp.2021.29.e21","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e21","url":null,"abstract":"Candesartan and olmesartan are angiotensin II receptor blockers (ARBs) used for the treatment of hypertension and heart failure. Quantitation methods for candesartan and olmesartan were developed using ultra-high performance liquid chromatography-tandem mass spectrometry following protein precipitation. Candesartan was separated using 5 mM ammonium formate (A) and 100% acetonitrile (B) and olmesartan was separated using 2 mM ammonium formate with 0.1% formic acid (A) and 100% acetonitrile (B). Separation was performed using an isocratic method with a Thermo hypersil GOLD C18 column. Electrospray ionization was used for analyte ionization and detection of candesartan, olmesartan, and the internal standards by multiple reaction monitoring. Developed method showed excellent linearity (r > 0.99) in the concentration range of 2-500 ng/mL for candesartan and 5-2,500 ng/mL for olmesartan. Accuracies were 86.70-108.8% for candesartan and 87.87-112.6% for olmesartan. These methods were able to successfully measure plasma candesartan or olmesartan concentrations in hypertensive patients. This study can be used for pharmacokinetic studies of candesartan or olmesartan in humans.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 4","pages":"226-238"},"PeriodicalIF":0.9,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/3d/tcp-29-226.PMC8718358.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39818624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Trends of clinical trials from 2017 to 2019 in Korea: an integrated analysis based on the Ministry of Food and Drug Safety (MFDS) and the Clinical Research Information Service (CRIS) registries. 2017 - 2019年韩国临床试验趋势:基于食品药品安全部(MFDS)和临床研究信息服务(CRIS)注册的综合分析

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-12-01 Epub Date: 2021-12-21 DOI: 10.12793/tcp.2021.29.e24

Ki Young Huh, Kyung-Sang Yu, Hyeong-Seok Lim, Hyungsub Kim

{"title":"Trends of clinical trials from 2017 to 2019 in Korea: an integrated analysis based on the Ministry of Food and Drug Safety (MFDS) and the Clinical Research Information Service (CRIS) registries.","authors":"Ki Young Huh, Kyung-Sang Yu, Hyeong-Seok Lim, Hyungsub Kim","doi":"10.12793/tcp.2021.29.e24","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e24","url":null,"abstract":"Public disclosure of approved clinical trials in a reliable registry can provide the transparency of the study. Although the registration of clinical trials has increased remarkably, the integrity of the data is not always satisfactory. In this study, we analyzed public clinical trial databases updated by the Ministry of Food and Drug Safety (MFDS) and Clinical Research Information Service (CRIS) registry to provide an overview of the trends of clinical trials approved between 2017 and 2019 in Korea. Information on clinical trials approved between January 1, 2017 and December 31, 2019 was collected from two databases. Trial information was categorized and summarized by study phase, therapeutic area, and location of the participating centers. A total of 655 to 715 clinical trials were newly approved annually by MFDS during the period from 2017 to 2019. Phase 1 clinical trials accounted for the largest proportion (31.0%), followed by phase 3 (29.5%), investigator-initiated trials (24.1%), phase 2 (14.6%), and phase 4 (0.5%). The number of clinical trials classified as an Antineoplastic and immunomodulating agent was the greatest (40.1%) regardless of the study phase. The similar result was obtained from CRIS registry where therapeutic area Neoplasms (15.9%) accounted for the largest number. The number of clinical trials performed in Seoul and Gyeonggi-do was approximately 70% of the total trials. In conclusion, our study provided a comprehensive overview of clinical trials in Korea from 2017 to 2019. The discrepancy between clinical trial registries could be resolved by introducing standardized database and guidelines.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 4","pages":"186-196"},"PeriodicalIF":0.9,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/23/tcp-29-186.PMC8718355.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

QTc prolongation in patients with COVID-19: a retrospective chart review. COVID-19患者QTc延长:回顾性图表回顾

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-12-01 Epub Date: 2021-11-25 DOI: 10.12793/tcp.2021.29.e20

Suphannika Prateepjarassaeng Pornwattanakavee, Watcharapong Priksri, Nattawut Leelakanok

{"title":"QTc prolongation in patients with COVID-19: a retrospective chart review.","authors":"Suphannika Prateepjarassaeng Pornwattanakavee, Watcharapong Priksri, Nattawut Leelakanok","doi":"10.12793/tcp.2021.29.e20","DOIUrl":"10.12793/tcp.2021.29.e20","url":null,"abstract":"Drug-induced corrected QT (QTc) prolongation can cause Torsade de Pointes (TdP) which leads to severe arrhythmia or sudden cardiac death. However, information on the prevalence of QTc prolongation in coronavirus disease 2019 (COVID-19) patients and risk factors is limited. A retrospective chart review was conducted in COVID-19 patients admitted to Chonburi Hospital from April to October 2020. The outcomes were the incidence of QTc prolongation and prevalence of risk factor QTc prolongation. We included 29 COVID-19 patients. After treatments were initiated, QTc prolongation occurred in 17 patients (58.62%). QT prolongation could be found as early as two days after the treatment initiation (median = 6 days interquartile range [IQR], 4-7). The median QTc interval in those 17 patients increased from 410 (IQR, 399.5-425.0) ms to 460 (453.50-466.50) ms, with the maximum QTc interval of 488 ms. They were treated with multiple drugs that were reported as a cause of QTc prolongation. 64.71% (n = 11) of them were treated with chloroquine. The median TdP risk score in patients with and without QTc prolongation was 3 (IQR, 2-3) and 2 (IQR, 1-2), respectively. The percentage of patients with comorbidities including atrial fibrillation, bradycardia, concomitant use of diuretics, diabetes, electrolyte imbalance was higher in patients with QTc prolongation. COVID-19 patients were treated with multiple drugs that were reported as a cause of QTc prolongation. COVID-19 patients with QTc prolongation had more comorbidities that are risk factors for QTc prolongation.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 4","pages":"197-205"},"PeriodicalIF":0.9,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/da/cf/tcp-29-197.PMC8718354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

A validated simple LC-MS/MS method for quantifying trimethylamine N-oxide (TMAO) using a surrogate matrix and its clinical application. 采用替代基质定量三甲胺n -氧化物(TMAO)的LC-MS/MS方法及其临床应用

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-12-01 Epub Date: 2021-11-23 DOI: 10.12793/tcp.2021.29.e19

Yufei Li, Jihyun Kang, Yujin Lee, Jae-Yong Chung, Joo-Youn Cho

{"title":"A validated simple LC-MS/MS method for quantifying trimethylamine N-oxide (TMAO) using a surrogate matrix and its clinical application.","authors":"Yufei Li, Jihyun Kang, Yujin Lee, Jae-Yong Chung, Joo-Youn Cho","doi":"10.12793/tcp.2021.29.e19","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e19","url":null,"abstract":"Trimethylamine N-oxide (TMAO) is a small molecular amine oxide generated from dietary choline and carnitine through intestinal microbial metabolism. Recently, TMAO has attracted much public attention as its role in disease progression has been proven in many clinical studies. The plasma concentration of TMAO in humans was found to be positively associated with the increased risk of many diseases including cardiovascular diseases and chronic kidney diseases. To achieve accurate and sensitive quantitation of TMAO for clinical applications, we established and validated a simple quantitative method using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. We constructed an eight-point calibration curve in an artificial surrogate matrix instead of the commonly used biological matrices to avoid interference from the endogenous TMAO. The calibration curve showed excellent linearity in the range of 1 to 5,000 ng/mL, with a correlation coefficient (R2) higher than 0.996 in each validation batch. Moreover, both the intra-day and inter-day assays achieved satisfactory precision and accuracy results ranging from 1.65-7.15% and 96.36-111.43%, respectively. Further, this method was cross-validated using a human plasma matrix and applied to a clinical pharmacology study. Overall, these results demonstrate that the developed quantitation method is applicable in clinical research for monitoring disease progression and evaluating drug effects.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 4","pages":"216-225"},"PeriodicalIF":0.9,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6c/ed/tcp-29-216.PMC8718357.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39818623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Medication selection for the treatment of acute infective diarrhea in Thai pharmacies: a qualitative study. 泰国药房治疗急性感染性腹泻的药物选择：一项定性研究。

IF 1.1

Translational and Clinical Pharmacology Pub Date : 2021-12-01 Epub Date: 2021-12-16 DOI: 10.12793/tcp.2021.29.e22

Nattawut Leelakanok, Arpa Petchsomrit, Janthima Methaneethorn, Suphannika Prateepjarassaeng Pornwattanakavee

{"title":"Medication selection for the treatment of acute infective diarrhea in Thai pharmacies: a qualitative study.","authors":"Nattawut Leelakanok, Arpa Petchsomrit, Janthima Methaneethorn, Suphannika Prateepjarassaeng Pornwattanakavee","doi":"10.12793/tcp.2021.29.e22","DOIUrl":"10.12793/tcp.2021.29.e22","url":null,"abstract":"World Health Organization (WHO) released the treatment manual of diarrhea in 2005. We aimed to investigate the rationale for selecting medications for acute infective diarrhea in Thai community pharmacies and to see if the selection complied with the WHO manual. A theoretical 18-year-old patient with acute infective diarrhea was used for interviews. The protocol and materials for the research were approved by Institutional Review Board. A total of 30 drugstore personnel were selected by convenience sampling and included. The first author manually coded, extracted for themes, and translated the transcript. Participants did not dispense oral rehydration salt because of the feeling that diarrhea was not severe. Absorbents were dispensed because they were perceived as the first-line medication for noninfective or mild diarrhea. Antibiotics were dispensed because of the concerns for the prognosis and the expected patient pressure. None provided zinc to the patient because of the lack of knowledge of the indication of zinc. We found that dispensing for acute infective diarrhea in Thai drugstores deviated from the WHO treatment guideline. The reasons were that the pharmacy personnel were not practicing evidence-based medicine, the lack of knowledge, the patient pressure, the unavailability of products, and the perceived availability of information in local guidelines.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 4","pages":"206-215"},"PeriodicalIF":1.1,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/6f/tcp-29-206.PMC8718353.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The use of real-world data in drug repurposing. 真实世界数据在药物再利用中的应用。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-09-01 Epub Date: 2021-09-27 DOI: 10.12793/tcp.2021.29.e18

Kyungsoo Park

{"title":"The use of real-world data in drug repurposing.","authors":"Kyungsoo Park","doi":"10.12793/tcp.2021.29.e18","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e18","url":null,"abstract":"Drug repurposing, or repositioning, is to identify new uses for existing drugs. Significantly reducing the costs and time-to-market of a medication, drug repurposing has been an alternative tool to accelerate drug development process. On the other hand, 'real world data (RWD)' has been also increasingly used to support drug development process owing to its better representing actual pattern of drug treatment and outcome in real world. In the healthcare domain, RWD refers to data collected from sources other than traditional clinical trials; for example, in electronic health records or claims and billing data. With the enactment of the 21st Century Cures Act, which encourages the use of RWD in drug development and repurposing as well, such increasing trend in RWD use will be expedited. In this context, this review provides an overview of recent progresses in the area of drug repurposing where RWD was used by firstly introducing the increasing trend and regulatory change in the use of RWD in drug development, secondly reviewing published works using RWD in drug repurposing, classifying them in the repurposing strategy, and lastly addressing limitations and advantages of RWDs.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 3","pages":"117-124"},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/58/tcp-29-117.PMC8492393.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Validation of LC-MS/MS method for determination of rosuvastatin concentration in human blood collected by volumetric absorptive microsampling (VAMS). LC-MS/MS法测定人血液中瑞舒伐他汀浓度的验证。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-09-01 Epub Date: 2021-08-31 DOI: 10.12793/tcp.2021.29.e13

Seol Ju Moon, Seon Eui Lee, Yong-Geun Kwak, Min-Gul Kim

{"title":"Validation of LC-MS/MS method for determination of rosuvastatin concentration in human blood collected by volumetric absorptive microsampling (VAMS).","authors":"Seol Ju Moon, Seon Eui Lee, Yong-Geun Kwak, Min-Gul Kim","doi":"10.12793/tcp.2021.29.e13","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e13","url":null,"abstract":"In light of the shift toward patient-centric clinical trials, a measure of simplifying blood collection process and minimizing the volume of blood samples is on the rise. Volumetric absorptive microsampling (VAMS) is a microsampling device developed for blood sampling in non-hospital settings, which enables accurate hematocrit-independent collection of 10 or 20 µL of whole blood with a simple finger prick. In this study, liquid chromatography (LC)-tandem mass spectrometry workflow for quantification of rosuvastatin after VAMS sampling was developed and validated. The VAMS sample was stabilized by matrix drying and the optimum LC conditions and extraction methods were used to reach adequate sensitivity with lower limit of quantification verified at 1 ng/mL in 10 µL of blood. The bioanalytical method to quantify rosuvastatin from 1 to 100 ng/mL in VAMS sample was qualified by specificity, carryover, linearity, within-run and between-run reproducibility and stability. Inaccuracy was less than ± 6% and imprecision was less than 10% after analyzing the samples on 5 different days at all concentration levels. In addition, the feasibility of delivery to the analytical laboratory after home sampling during the guaranteed stability period of 10 days at room temperature was confirmed by evaluating concentration changes after VAMS sampling without adding pH buffer. Our results suggest that VAMS sampling did not have an effect on the stability of rosuvastatin, and it is a viable option for simple and accurate blood collection at home.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 3","pages":"125-134"},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/24/tcp-29-125.PMC8492392.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Comprehensive analysis of important pharmacogenes in Koreans using the DMET™ platform. 使用DMET™平台对韩国人重要药原基因进行综合分析。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-09-01 Epub Date: 2021-09-02 DOI: 10.12793/tcp.2021.29.e14

Byungwook Kim, Deok Yong Yoon, SeungHwan Lee, In-Jin Jang, Kyung-Sang Yu, Joo-Youn Cho, Jaeseong Oh

{"title":"Comprehensive analysis of important pharmacogenes in Koreans using the DMET™ platform.","authors":"Byungwook Kim, Deok Yong Yoon, SeungHwan Lee, In-Jin Jang, Kyung-Sang Yu, Joo-Youn Cho, Jaeseong Oh","doi":"10.12793/tcp.2021.29.e14","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e14","url":null,"abstract":"Genetic polymorphisms of enzymes and transporters associated with the absorption, distribution, metabolism, and elimination (ADME) of drugs are one of the major factors that contribute to interindividual variations in drug response. In the present study, we aimed to elucidate the pharmacogenetic profiles of the Korean population using the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET™) platform. A total of 1,012 whole blood samples collected from Korean subjects were genotyped using the DMET™ plus microarray. In total, 1,785 single nucleotide polymorphism (SNP) markers for 231 ADME genes were identified. The genotype and phenotype of 13 clinically important ADME genes implemented in the Clinical Pharmacogenetics Implementation Consortium guidelines were compared among different ethnic groups. Overall, the genotype frequencies of the Korean population were similar to those of the East Asian population. Several genes, notably CYP2C19 and VKORC1, showed marked differences in Koreans compared to Europeans (EURs) or Africans (AFRs). The percentage of CYP2C19 poor metabolizers was 15% in Koreans and less than 3% in EURs or AFRs. The frequencies of causative SNPs of the VKORC1 gene for the low warfarin dose phenotype were 90%, 60%, and 10% in Koreans, EURs and AFRs, respectively. Our findings can be utilized for optimal pharmacotherapy in Korean patients.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 3","pages":"135-149"},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/eb/tcp-29-135.PMC8492395.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The possibility of low isomerization of β-lapachone in the human body. β-lapachone在人体内低异构化的可能性。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-09-01 Epub Date: 2021-09-24 DOI: 10.12793/tcp.2021.29.e16

Kyung Min Lee, Mi-Ri Gwon, Hae Won Lee, Sook Jin Seong, Young-Ran Yoon

{"title":"The possibility of low isomerization of β-lapachone in the human body.","authors":"Kyung Min Lee, Mi-Ri Gwon, Hae Won Lee, Sook Jin Seong, Young-Ran Yoon","doi":"10.12793/tcp.2021.29.e16","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e16","url":null,"abstract":"β-Lapachone has been reported to have anticancer and various other therapeutic effects, but is limited in clinical applications by its low bioavailability. pH-Dependent isomerization can be suggested as one plausible factor influencing its low bioavailability. Since it is known that β-lapachone is converted to its isomer, α-lapachone in hydrochloric acid (HCl) solution, isomerization in the human body may be driven by HCl in the gastric fluid. The purpose of this study was to evaluate the possibility of isomerization of β-lapachone in the human body. Chemical reactions were conducted using simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.5) at 37°C. β-Lapachone was observed in SGF at 37°C for 1 hour and SIF for 3 hours. In addition, biofluid analysis was performed on plasma samples 1 hour and 4 hours, and on urine sample 12 hours after oral administration of 100 mg MB12066, a synthetic β-lapachone, in healthy adult male. All samples were analyzed using liquid chromatography-tandem mass spectrometry. Only β-lapachone peaks existed in the spectra obtained from SGF and SIF. No isomerization of β-lapachone was observed in the analysis of any of the human samples. In the current study, the possibility of pH-dependent isomerization of β-lapachone in the human body was not confirmed.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 3","pages":"160-170"},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/12/tcp-29-160.PMC8492396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of the pharmacokinetics and pharmacodynamics of YH4808 in healthy subjects for defining an appropriate dosing regimen. 比较YH4808在健康受试者体内的药代动力学和药效学，以确定合适的给药方案。

IF 0.9

Translational and Clinical Pharmacology Pub Date : 2021-09-01 Epub Date: 2021-09-17 DOI: 10.12793/tcp.2021.29.e15

Sukyong Yoon, EunSil Oh, Min Soo Park, Seong Bok Jang, Hae Mi Byun, Hyeonsoo Park, Heeyoung Kim, Choon Ok Kim

{"title":"Comparison of the pharmacokinetics and pharmacodynamics of YH4808 in healthy subjects for defining an appropriate dosing regimen.","authors":"Sukyong Yoon, EunSil Oh, Min Soo Park, Seong Bok Jang, Hae Mi Byun, Hyeonsoo Park, Heeyoung Kim, Choon Ok Kim","doi":"10.12793/tcp.2021.29.e15","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e15","url":null,"abstract":"YH4808 is a novel potassium-competitive acid blocker developed for gastric acid-related disorders. Previous studies indicate its potential to improve symptoms of gastric acid-related disorders. The current study was aimed to find the optimal regimen of YH4808 for night time pH control. This study was performed in two parts. Each was a randomized, open-label, active-controlled, multiple-doses, two-treatment, two-period crossover study conducted in 20 healthy Korean volunteers. Subjects were randomly assigned to one of the four groups. The three groups received different dosage regimens of YH4808 (100 mg twice a day, 200 mg once a day, or 200 mg twice a day), and the fourth group received esomeprazole 40 mg twice a day. The pharmacokinetic parameters demonstrated that the systemic exposure of YH4808 increased in a dose-proportional manner. The difference in the proportion of time above pH 4 over 24 h from the baseline was the greatest in the group receiving YH4808 200 mg twice a day. The values of the area under the effect curve at night time (12 A.M.-7 A.M.) were higher in all YH4808 groups than in the esomeprazole group. However, the differences among the YH4808 groups were not statistically significant (p > 0.05). YH4808 exhibited potential for better pH control during the night in comparison to esomeprazole. The optimal regimen for night time pH control among all the YH4808 regimens was 200 mg twice a day.Trial registration: ClinicalTrials.gov Identifier: NCT01761513.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 3","pages":"150-159"},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/18/tcp-29-150.PMC8492394.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1