Translational and Clinical Pharmacology最新文献

{"title":"Pharmacokinetic properties and bioequivalence of gefitinib 250 mg in healthy Korean male subjects.","authors":"Seol Ju Moon,&nbsp;Yunjeong Kim,&nbsp;Ji-Young Jeon,&nbsp;Shin-Jung Park,&nbsp;Yong-Geun Kwak,&nbsp;Min-Gul Kim","doi":"10.12793/tcp.2021.29.e17","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e17","url":null,"abstract":"<p><p>Gefitinib is an anti-cancer drug used to treat non-small cell lung cancer. The objective of this study was to compare the pharmacokinetics and evaluate the bioequivalence of 2 orally administered gefitinib 250 mg tablets in healthy Korean subjects. A randomized, open-label, single-dose, crossover bioequivalence study was conducted. A total of 50 healthy male volunteers were randomized into 2 sequence groups. During each treatment, the subjects received the test or reference formulation of 250 mg gefitinib with a washout period of 21 days. The plasma samples were collected at pre-dose and up to 144 hours post-dose, and plasma drug concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated, and the formulations were considered as bioequivalent if the 90% confidence intervals (CIs) of the geometric mean ratios were within the bioequivalence limits of 0.8 to 1.25. Forty-one subjects completed the study and were included in the pharmacokinetic analysis. The 90% CIs of the geometric mean ratios of the test formulation to the reference formulation were 0.8115 to 0.9993 for maximum plasma concentration and 0.9119 to 1.0411 for area under the plasma concentration versus time curve from dosing to the last measurable concentration. There were no serious or unexpected adverse events during the study. In healthy Korean adult subjects, the test and reference formulations of gefitinib 250 mg had similar pharmacokinetic parameters and similar plasma concentration-time profiles. The test formulation of gefitinib met the regulatory criteria for assuming bioequivalence. Both formulations were safe and well-tolerated.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 3","pages":"171-179"},"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/52/ec/tcp-29-171.PMC8492391.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498513","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}

{"title":"Insulin sensitization causes accelerated sinus nodal dysfunction through autophagic dysregulation in hypertensive mice.","authors":"Minna Woo,&nbsp;Minsuk Kim","doi":"10.12793/tcp.2021.29.e9","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e9","url":null,"abstract":"<p><p>Insulin sensitizers, while effective in glucose-lowering for diabetes control, are linked to an increased risk of heart disease through mechanisms that are not well understood. In this study, we investigated the molecular mechanisms underlying the effects of insulin sensitization on cardiac sinus node dysfunction. We used pharmacologic or genetic approaches to enhance insulin sensitivity, by treating with pioglitazone or rosiglitazone, or through phosphatase and tensin homolog (<i>PTEN</i>) deletion in cardiomyocytes respectively. We employed an angiotensin II (Ang II)-induced hypertensive animal model which causes sinus node dysfunction and accumulation of oxidized calcium/calmodulin-dependent protein kinase II (CaMKII), which also serves as a biomarker for this defect. While neither <i>PTEN</i> deficiency nor insulin sensitizers caused sinus node dysfunction in normotensive mice, both accelerated the onset of sinus node dysfunction and CaMKII oxidation in hypertensive mice. These abnormalities were accompanied by a significant defect in autophagy as revealed by unc-51 like autophagy activating kinase 1 (ULK1) signaling. Indeed, mice deficient in <i>ulk1</i> in cardiomyocytes and the sinus node also showed early onset of slow atrial impulse conduction with frequent sinus pauses and upregulated CaMKII oxidation following Ang II infusion similar to that seen with <i>PTEN</i> deficiency, or treatment with insulin sensitizers. To further elucidate the role of autophagy in sinus node dysfunction, we treated mice with a peptide D-Tat-beclin1 that enhanced autophagy, which significantly abrogated the frequent sinus pauses and accumulation of oxidized CaMKII induced by insulin sensitizers treatment, or <i>PTEN</i> deficiency in hypertensive animals. Together, these findings provide clear evidence of the detrimental cardiac effects of insulin sensitization that occurs through failure of autophagy-mediated proteolytic clearance.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 2","pages":"92-106"},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/13/tcp-29-92.PMC8255547.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39162865","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}

{"title":"Associations between HLA-A, -B, and -C alleles and iodinated contrast media-induced hypersensitivity in Koreans.","authors":"Eun-Young Kim,&nbsp;Seok Jin Choi,&nbsp;Jong-Lyul Ghim,&nbsp;Mi-Yeong Kim,&nbsp;Jung Eun Seol,&nbsp;Minkyung Oh,&nbsp;Chan Sun Park,&nbsp;Jae-Gook Shin","doi":"10.12793/tcp.2021.29.e10","DOIUrl":"10.12793/tcp.2021.29.e10","url":null,"abstract":"<p><p>A common cause of drug hypersensitivity reactions is iodinated contrast media (ICM). ICM-induced hypersensitivity had been considered to be a non-immunological reaction, but evidence for an immunological mechanism has increased recently. Thus, we evaluated whether HLA-A, -B, and -C alleles were associated with ICM-induced hypersensitivity. In total, 126 patients who underwent contrast-enhanced computed tomography studies through outpatient clinics at a tertiary referral hospital between 2008 and 2012 were assessed. Sixty-one patients experienced ICM-induced hypersensitivity and the remainder, 65, were ICM-tolerant patients (control). ICM-induced hypersensitivity patients showed 51 with immediate, 7 with non-immediate, 3 with both or mixed type. HLA-A, -B, and -C genotyping was performed using a PCR sequence-based typing method. Four kinds of ICM were used: iopromide, iohexol, iobitridol, and iodixanol. The most used ICM among the hypersensitivity patients was iopromide. Significant difference in the frequency of <i>HLA-B*58:01</i> (odds ratios [OR], 3.90; <i>p</i> = 0.0200, 95% confidence interval [CI], 1.16-13.07) was observed between ICM-induced immediate hypersensitivity and control. There were statistically significant differences in the frequencies of the <i>HLA-B*38:02</i> (OR, 10.24; <i>p</i> = 0.0145; 95% CI, 1.09-96.14) and <i>HLA-B*58:01</i> (OR, 3.98; <i>p</i> = 0.0348; 95% CI, 1.03-15.39) between iopromide-induced immediate hypersensitivity and control. The mechanism of ICM-induced hypersensitivity remains unknown, but this study showed associations, although weak, with <i>HLA-B*58:01</i> alleles for ICM-induced immediate hypersensitivity and <i>HLA-B*38:02 and HLA-B*58:01</i> for iopromide-induced immediate hypersensitivity as risk predictors. Further studies are needed to validate the associations in larger samples and to identify the functional mechanism behind these results.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 2","pages":"107-116"},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/18/tcp-29-107.PMC8255545.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39162866","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}

{"title":"Predicting human pharmacokinetics from preclinical data: clearance.","authors":"Dong-Seok Yim,&nbsp;Soo Hyeon Bae,&nbsp;Suein Choi","doi":"10.12793/tcp.2021.29.e12","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e12","url":null,"abstract":"<p><p>We have streamlined known <i>in vitro</i> methods used to predict the clearance (CL) of small molecules in humans in this tutorial. There have been many publications on <i>in vitro</i> methods that are used at different steps of human CL prediction. The steps from initial intrinsic CL measurement <i>in vitro</i> to the final application of the well-stirred model to obtain predicted hepatic CL (CL_H) are somewhat complicated. Except for the experts on drug metabolism and PBPK, many drug development scientists found it hard to figure out the entire picture of human CL prediction. To help readers overcome this barrier, we introduce each method briefly and demonstrate its usage in the chain of related equations destined to the CL_H. Despite efforts in the laboratory steps, huge <i>in vitro</i> (predicted CL_H)-<i>in vivo</i> (observed CL_H) discrepancy is not rare. A simple remedy to this discrepancy is to correct human predicted CL_H using the ratio of <i>in vitro-in vivo</i> CL_H obtained from animal species.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 2","pages":"78-87"},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/31/26/tcp-29-78.PMC8255549.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39163329","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}

{"title":"Acetaminophen-induced anaphylaxis: a case report.","authors":"Jung Sunwoo,&nbsp;Hyungsub Kim,&nbsp;Kyun-Seop Bae","doi":"10.12793/tcp.2021.29.e8","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e8","url":null,"abstract":"<p><p>Acetaminophen is known to be generally safe, and the occurrence of anaphylaxis due to acetaminophen has been rarely reported. We report a case of acetaminophen-induced anaphylaxis in a healthy male subject who participated in a clinical trial on the pharmacokinetics of ibandronate. The subject had not experienced an allergic reaction to acetaminophen prior to this incident. The patient received 1300 mg oral acetaminophen at about 12 hours after receiving 150 mg ibandronate. After about 10 minutes, the subject developed whole-body urticaria and hypotension. The temporal association suggested that the anaphylaxis was due to acetaminophen and not ibandronate. Anaphylaxis could occur due to acetaminophen even in the absence of allergic reactions in the first dosing.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 2","pages":"88-91"},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/21/tcp-29-88.PMC8255548.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39163330","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}

{"title":"Adequacy of safety data for regulatory approval of pediatric indication through extrapolation algorithm.","authors":"Min Soo Park","doi":"10.12793/tcp.2021.29.e11","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e11","url":null,"abstract":"https://tcpharm.org This commentary deals with the realistic difficulty arising from the haziness as to what safety data should mean, especially for regulatory authorities to feel confident that approval of new drug indications for pediatric populations could be endowed, and when you were guided that complete extrapolation of adult efficacy data would be possible with an additional pharmacokinetic (PK) study, but safety data cannot be extrapolated.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 2","pages":"73-77"},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2e/4c/tcp-29-73.PMC8255546.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39163328","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}

{"title":"A meta-analysis: efficacy and safety of anti-epileptic drugs prescribed in Korea as monotherapy and adjunctive treatment for patients with focal epilepsy.","authors":"JuYeun Jeon,&nbsp;Jaeseong Oh,&nbsp;Kyung-Sang Yu","doi":"10.12793/tcp.2021.29.e1","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e1","url":null,"abstract":"<p><p>Focal epilepsy is the most common type of epilepsy in Korea, and anti-epileptic drugs (AEDs) are the main treatment option for patients. This study aimed to compare the efficacy and safety of AEDs for focal epilepsy through a meta-analysis. The AEDs prescribed in Korea as monotherapy and adjunctive treatment for patients with focal epilepsy were included for analysis. Relevant articles were searched for randomized clinical trials of AEDs and treatment outcomes were analyzed on the basis of the 50% responder rate, seizure-free rate, treatment withdrawal rate, and emergence rates of adverse events (AEs). The odds ratios (ORs) and their 95% confidence intervals (CI) of study outcome were calculated using combined data from multiple studies. A total of 47 studies were included in the meta-analysis. The seizure-free rate, treatment withdrawal rate, and AE rate were not significantly different among the AEDs recommended for monotherapy. Among the AEDs recommended for adjunctive treatment, topiramate and oxcarbazepine yielded the highest OR in comparison with placebo for each efficacy parameter: the 50% responder rate for topiramate = 6.42 (3.76-11.6) and the seizure-free rate for oxcarbazepine = 32.7 (6.05-899). The third-generation AEDs (brivaracetam and perampanel) yielded relatively better safety outcomes than other AEDs. In general, the 50% responder rate and treatment withdrawal rate tended to increase as the dose of the AEDs increased. The results from the current meta-analysis of the efficacy and safety data of various AEDs may provide insight into optimal pharmacotherapy for the treatment of focal epilepsy.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 1","pages":"6-20"},"PeriodicalIF":0.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/a6/tcp-29-6.PMC8020359.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38875102","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}

{"title":"Cognitive improvement effect of gintonin might be associated with blood-brain barrier permeability enhancement: dynamic contrast-enhanced MRI pilot study.","authors":"Woo-Jin Lee, Yong-Won Shin, Hyeyeon Chang, Hye-Rim Shin, Won-Woo Kim, Seok-Won Jung, Seung-Hong Choi, Manho Kim, Seung-Yeol Nah","doi":"10.12793/tcp.2021.29.e2","DOIUrl":"10.12793/tcp.2021.29.e2","url":null,"abstract":"<p><p>Along with the multiple neuroprotective effect, recent studies suggest that gintonin might increase the blood brain barrier permeability. We evaluated the effect of gintonin on the vascular permeability changes in different brain segments, using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). In this 8-week, randomized, open label pilot study, ten participants with subjective memory impairment but preserved cognitive function assigned to gintonin-enriched fraction (GEF) 300 mg/day or placebo groups. Korean versions of the Alzheimer's disease assessment scale (ADAS-K) and DCE-MRI parameters including K^trans and V_p in different brain segments were evaluated at baseline and at 8 weeks after treatment. Nine participants completed the study protocol. No adverse events occurred during the observation period for 8 weeks in both groups. Following gintonin administration, increment trends of the brain permeability that did not reach a statistical significance were observed in the left hippocampus (K^trans and V_p, both, <i>p</i> = 0.062), left thalamus and in left putamen (K^trans, <i>p</i> = 0.062), and left insula and right amygdala (V_p, <i>p</i> = 0.062), but not in the control placebo group. The increment of the K^trans value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = -0.900, <i>p</i> = 0.037). Gintonin might enhance the blood-brain barrier (BBB) permeability in the brain structures involved in cognitive functions. Further efficacy exploration for the synergistic effect of gintonin's BBB permeability enhancement to its other cognitive enhancing mechanisms are warranted.</p><p><strong>Trial registration: </strong>Clinical Research Information Service Identifier: KCT0003418.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 1","pages":"21-32"},"PeriodicalIF":0.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/3f/tcp-29-21.PMC8020362.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38875103","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}

{"title":"Physiologically-based pharmacokinetic model for clozapine in Korean patients with schizophrenia.","authors":"Joomi Lee,&nbsp;Min-Gul Kim,&nbsp;Hyeon-Cheol Jeong,&nbsp;Kwang-Hee Shin","doi":"10.12793/tcp.2021.29.e3","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e3","url":null,"abstract":"<p><p>Clozapine has been used as a treatment of schizophrenia. Despite its large interindividual variability, few reports addressed the physiologically-based pharmacokinetic modeling and simulation (PBPK M&S) of clozapine in patients. This study aimed to develop a PBPK M&S of clozapine in Korean patients with schizophrenia. PBPK modeling for clozapine was constructed using a population-based PBPK platform, the SimCYP^® Simulator (V19; Certara, Sheffield, UK). The PBPK model was developed by optimizing the physiological parameters of the built-in population and compound libraries in the SimCYP^® Simulator. The model verification was performed with the predicted/observed ratio for pharmacokinetic parameters and visual predictive checks (VPCs) plot. Simulations were performed to predict toxicities according to dosing regimens. From published data, 230 virtual trials were simulated for each dosing regimen. The predicted/observed ratio for the area under the curve and peak plasma concentration was calculated to be from 0.78 to 1.34. The observation profiles were within the 5th and 95th percentile range with no serious model misspecification through the VPC plot. A significant impact on age and gender was found for clozapine clearance. The simulation results suggested that 150 mg twice a day and 150 mg three times a day of clozapine have toxicity concerns. In conclusion, a PBPK model was developed and reasonable parameters were made from the data of Korean patients with schizophrenia. The provided model might be used to predict the pharmacokinetics of clozapine and assist dose adjustment in clinical settings.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 1","pages":"33-44"},"PeriodicalIF":0.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/6a/tcp-29-33.PMC8020364.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38875104","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}

{"title":"Pharmacokinetic comparison between a fixed-dose combination of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg and a corresponding loose combination of fimasartan/amlodipine 60/25 mg and hydrochlorothiazide 25 mg in healthy subjects.","authors":"Jihyun Jung,&nbsp;Soyoung Lee,&nbsp;Jaeseong Oh,&nbsp;SeungHwan Lee,&nbsp;In-Jin Jang,&nbsp;Donghwan Lee,&nbsp;Kyung-Sang Yu","doi":"10.12793/tcp.2021.29.e5","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e5","url":null,"abstract":"<p><p>For the treatment of hypertension, fixed-dose combinations (FDCs) of antihypertensive drugs can provide complementary benefits from improved compliance and cost-effectiveness compared with loose combinations of corresponding drugs. A new FDC of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg is undergoing clinical development. A randomized, open-label, single-dose, 3-period, 3-sequence, partially replicated crossover phase 1 study was conducted to compare the pharmacokinetics (PKs) between the FDC of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg and a loose combination of a dual-combination FDC (fimasartan/amlodipine 60/10 mg) and hydrochlorothiazide 25 mg. Sixty healthy subjects were randomized, and 55 subjects completed the study. Serial blood samples were collected, and plasma concentrations of fimasartan, amlodipine and hydrochlorothiazide were measured to analyze PK parameters. The PK profiles of the FDC were similar to those of the loose combinations. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to loose combinations for the maximum plasma concentration (C_max) and area under the curve until the last measurable time point (AUC_last) were within the conventional bioequivalent range of 0.80 to 1.25. The GMRs and 90% CIs of fimasartan, amlodipine and hydrochlorothiazide were 1.0163 (0.8681-1.1898), 0.9595 (0.9256-0.9946), and 1.1294 (1.0791-1.1821) for C_max and 1.0167 (0.9347-1.1059), 0.9575 (0.9317-0.9841), and 1.0561 (1.0170-1.0967) for AUC_last, respectively. Both the FDC and loose combinations were well tolerated. In conclusion, the FDC of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg showed similar PK profiles to those of the corresponding loose combination, and both treatments were well tolerated.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"29 1","pages":"53-64"},"PeriodicalIF":0.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/d5/tcp-29-53.PMC8020363.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38874566","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}