British journal of clinical pharmacology最新文献_第3页

Influence of gut bile acid composition on the glucose-lowering effect and safety of metformin.

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-12-02 DOI: 10.1111/bcp.16358

Deok Yong Yoon, Jungeun Kim, Joo-Youn Cho, Jae-Yong Chung

{"title":"Influence of gut bile acid composition on the glucose-lowering effect and safety of metformin.","authors":"Deok Yong Yoon, Jungeun Kim, Joo-Youn Cho, Jae-Yong Chung","doi":"10.1111/bcp.16358","DOIUrl":"https://doi.org/10.1111/bcp.16358","url":null,"abstract":"Aims: This study evaluates how changes in intestinal bile acid composition, induced by cholestyramine, a bile acid sequestrant, affect metformin's pharmacodynamics (PD).Methods: An open-label, 2-period 1-sequence crossover study was conducted with healthy male adults. Each period consisted of both before and after metformin treatments. Cholestyramine was administered during the second period to change the bile acid pool. For, PD assessment, an oral glucose tolerance test was conducted at each treatment in both periods. Metformin was administered 3 times during each period, and cholestyramine was administered 3 times per day for 7 days during the second period. Maximum serum glucose concentration, area under the glucose concentration curve and homeostatic model assessment of insulin resistance were calculated. Baseline-corrected PD parameters were derived by subtracting pre-metformin values from post-metformin values. Lipid and panels and bile acid profiles in stool were measured. Adverse events were monitored throughout the study.Results: Fourteen subjects completed the study. The mean values of 3 PD parameters were all decreased after metformin administration in both periods. Cholestyramine administration led to a further decrease in baseline-corrected PD parameters, significantly reducing the area under the glucose concentration curve by 44.7%. Diarrhoea, the most common adverse event, was reported in 10 subjects during the metformin alone treatment and in 1 subject during the cholestyramine combined treatment (P < .01).Conclusion: Cholestyramine affected the glucose-lowering effect of metformin by the possible change in the bile acid pool in the gut, and metformin-associated diarrhoea was improved by cholestyramine.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selected Abstracts from Pharmacology 2024.

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-12-02 DOI: 10.1111/bcp.16336

引用次数: 0

Between Scylla and Charybdis: Navigating heart failure management in complex older adults.

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-11-29 DOI: 10.1111/bcp.16357

Lorenz Van der Linden, Ross Tsuyuki

引用次数: 0

Exploring the factors associated with difficulties in extracting tablets or capsules from press-through-package sheets.

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-11-28 DOI: 10.1111/bcp.16355

Masami Tsuchiya, Shungo Imai, Masaki Asano, Yuri Shimizu, Hayato Kizaki, Yukiko Ito, Makoto Tsuchiya, Ryoko Kuriyama, Nao Yoshida, Masanori Shimada, Takanori Sando, Tomo Ishijima, Satoko Hori

{"title":"Exploring the factors associated with difficulties in extracting tablets or capsules from press-through-package sheets.","authors":"Masami Tsuchiya, Shungo Imai, Masaki Asano, Yuri Shimizu, Hayato Kizaki, Yukiko Ito, Makoto Tsuchiya, Ryoko Kuriyama, Nao Yoshida, Masanori Shimada, Takanori Sando, Tomo Ishijima, Satoko Hori","doi":"10.1111/bcp.16355","DOIUrl":"https://doi.org/10.1111/bcp.16355","url":null,"abstract":"Exploring factors related to difficulties in extracting tablets or capsules from press-through-packages is essential for optimizing the dosage form. To achieve this, the involvement of patient insight is important. In the present study, the preferences of patients regarding drugs that are difficult to extract from their packaging were collected using an electronic medication notebook ('harmo®') based on dispensing data. We found that approximately 30% of respondents had difficulty removing tablets or capsules from their packaging, with 125 specific drugs identified as 'hard to push out'. Independent factors related to 'hard-to-push-out' drugs were female sex and feeling of weakness in the hands or fingers. Furthermore, several 'hard-to-push-out' drugs had characteristics such as a spherical shape or small major axis or small major axis drug-to-pocket size ratio. The findings of this study may help improve the quality of drug packaging, thus enhancing the patients' medication experience.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Issue Highlights

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-11-27 DOI: 10.1111/bcp.16348

引用次数: 0

Safety pharmacology of acute mescaline administration in healthy participants. 在健康参与者中急性服用麦司卡林的安全药理学。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-11-25 DOI: 10.1111/bcp.16349

Aaron Klaiber, Mélusine Humbert-Droz, Laura Ley, Yasmin Schmid, Matthias E Liechti

{"title":"Safety pharmacology of acute mescaline administration in healthy participants.","authors":"Aaron Klaiber, Mélusine Humbert-Droz, Laura Ley, Yasmin Schmid, Matthias E Liechti","doi":"10.1111/bcp.16349","DOIUrl":"https://doi.org/10.1111/bcp.16349","url":null,"abstract":"Aims: Psychedelics, including mescaline, may serve as novel treatments for depression and anxiety. However, data is scarce on the safety of mescaline.Methods: The present pooled analysis included two double-blind, randomized, placebo-controlled studies with a total of 48 participants and 96 mescaline administrations. Single oral-dose administrations (n = 16/dose) of mescaline at doses of 100-800 mg were used. Acute subjective and autonomic effects and acute and subacute adverse effects were recorded. Liver and kidney function, blood cell counts, and \"flashbacks\" were documented at the end of the studies.Results: Positive subjective effects dose-dependently increased and were higher than negative subjective effects for all mescaline doses. Autonomic effects increased moderately. Systolic blood pressure remained < 180 mmHg in all participants. Of all mescaline administrations, diastolic blood pressure > 100 mmHg was measured in 6%, heart rate > 100 beats/min was measured in 3% and body temperature > 38 °C was measured in 5%. The total number of acute adverse effects was 51, 12, 179, 143, 165 and 180 at 100, 200, 300, 400, 500 and 800 mg doses of mescaline, respectively. Nausea was dose-limiting. Kidney and liver function and blood cell counts remained normal. \"Flashbacks\" were reported after 2% of all mescaline administrations.Conclusions: These findings suggest that the administration of single mescaline doses up to 800 mg are safe in a controlled clinical setting with regard to acute psychological and physical harm in healthy participants.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Applying the estimand framework to clinical pharmacology trials with a case study in bioequivalence. 以生物等效性为例，在临床药理试验中应用估计值框架。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-11-25 DOI: 10.1111/bcp.16347

Helle Lynggaard, Sue McKendrick, Mark Baird, Essam Kerwash, Vivian Lanius, Florian Lasch, David Wright

{"title":"Applying the estimand framework to clinical pharmacology trials with a case study in bioequivalence.","authors":"Helle Lynggaard, Sue McKendrick, Mark Baird, Essam Kerwash, Vivian Lanius, Florian Lasch, David Wright","doi":"10.1111/bcp.16347","DOIUrl":"https://doi.org/10.1111/bcp.16347","url":null,"abstract":"The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use has published an addendum on estimands and sensitivity analysis in clinical trials along with related training materials. These define an estimand as a precise description of the treatment effect that reflects the scientific question of interest. In December 2022, the US Food and Drug Administration released draft guidance recommending estimands of interest be specified in bioequivalence trial protocols. However, experience in implementing estimands in clinical pharmacology trials is limited and so we introduce estimands and provide step-by-step considerations about the estimand thinking process in this setting. We also describe a particular case study, a bioequivalence trial, illustrating how the estimand framework can provide transparency and alignment throughout the design, conduct and analysis of the trial. This involves discussion of how to identify and handle intercurrent events, which are events that can affect interpretation of the drug or metabolite endpoints. Furthermore, we discuss the broader applicability of the estimand framework to other clinical pharmacology trials. Finally, we encourage further discussion between industry, academia, regulators and the International Council for Harmonisation on whether the estimand framework should be considered in all clinical pharmacology regulatory guidance documents.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PBPK modelling for the evaluation of drug-drug interaction between meropenem and valproic acid. 用于评估美罗培南和丙戊酸之间药物相互作用的 PBPK 模型。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-11-22 DOI: 10.1111/bcp.16350

Hongrui Liu, Yiqun Yu, Yulin Qin, Bing Han

{"title":"PBPK modelling for the evaluation of drug-drug interaction between meropenem and valproic acid.","authors":"Hongrui Liu, Yiqun Yu, Yulin Qin, Bing Han","doi":"10.1111/bcp.16350","DOIUrl":"https://doi.org/10.1111/bcp.16350","url":null,"abstract":"Aims: The present study aimed to quantitatively investigate the potential drug-drug interaction (DDI) mechanism between meropenem (MEPM) and valproic acid (VPA).Methods: In the present study, we firstly developed a physiologically based pharmacokinetic (PBPK) model of MEPM and VPA. The verified PBPK model was then used to quantitatively investigate the potential DDI between MEPM and VPA. The effect of genetic polymorphisms of acylpeptide hydrolase (APEH) on DDI was also evaluated.Results: In our simulation, the plasma concentration of hydrolysate of VPAG decreased to 63% when combined with MEPM. Total plasma concentration of VPA before carbapenem use was 53.61 mg/L, whereas it was 45.42 mg/L during carbapenem use. The inhibition of hydrolysis of VPAG by MEPM alone could not result in a rapid and substantial decrease in the plasma concentration of VPA. Parameter sensitivity analysis showed that the changes of absorption played an important role in the maximum plasma concentration (Cmax) of VPA, whereas area under the plasma concentration-time profile (AUC) was more susceptible to elimination changes. In addition, a decrease in APEH activity had little impact on the plasma pharmacokinetics of VPA.Conclusions: The DDI between MEPM and VPA might be a comprehensive result of multiple factors. On the basis of our simulation, interval medication of MEPM injection and VPA immediate release tablet at 4-6 h timed interval was recommended, or intravenous administration of VPA solution was preferred when combination regimen was necessary in a clinical setting.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration. 肾功能受损者单次口服布仑索卡替后的药代动力学。

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-11-22 DOI: 10.1111/bcp.16344

Sam Au Yeung, Daniel S Stein, Thomas C Marbury, Helen Usansky

{"title":"The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration.","authors":"Sam Au Yeung, Daniel S Stein, Thomas C Marbury, Helen Usansky","doi":"10.1111/bcp.16344","DOIUrl":"https://doi.org/10.1111/bcp.16344","url":null,"abstract":"Aim: Brensocatib is an oral, selective, competitive and reversible dipeptidyl peptidase 1 inhibitor in development for the treatment of bronchiectasis. This study evaluated the pharmacokinetics (PKs), safety and tolerability of brensocatib in participants with varying degrees of renal impairment and normal renal function.Methods: In this phase 1, multicentre, open-label study, 28 participants with mild, moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] 60 to <90, 30 to <60 and 15 to <30 mL/min/1.73 m2, respectively) or normal renal function (≥90 mL/min/1.73 m2) received a single oral 25-mg dose of brensocatib. Blood samples were collected to measure brensocatib PKs at predetermined time points over the 14-day study period. PK parameters were derived using noncompartmental methods.Results: Demographic and baseline characteristics were similar across groups. There were no significant differences between groups in brensocatib PK parameters. The mean coefficient of variation (CV) of elimination half-life of brensocatib was 37.0 (15.3), 42.8 (21.7), 36.3 (22.9) and 39.1 (17.8) h for mild, moderate, severe and normal renal function groups, respectively. Single-dose brensocatib was quickly absorbed; all groups had a median time to maximum observed plasma concentration of 1 h. Regression model analyses indicated no significant relationships between selected brensocatib PK parameters and eGFR. No treatment-emergent adverse events were reported during the study.Conclusion: Single-dose brensocatib was well tolerated. The study data do not indicate a significant effect of renal impairment on brensocatib elimination and systemic exposure, suggesting that dose adjustment of brensocatib is not necessary in participants with renal impairment.Clinical trial registration number: NCT05673603.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 3.1 3区医学

British journal of clinical pharmacology Pub Date : 2024-11-21 DOI: 10.1111/bcp.16335

Monika Berezowska, Isaac S Hayden, Andrew M Brandon, Arsenii Zats, Mehzabin Patel, Shelby Barnett, Kayode Ogungbenro, Gareth J Veal, Alaric Taylor, Jugal Suthar

{"title":"Recommended approaches for integration of population pharmacokinetic modelling with precision dosing in clinical practice.","authors":"Monika Berezowska, Isaac S Hayden, Andrew M Brandon, Arsenii Zats, Mehzabin Patel, Shelby Barnett, Kayode Ogungbenro, Gareth J Veal, Alaric Taylor, Jugal Suthar","doi":"10.1111/bcp.16335","DOIUrl":"https://doi.org/10.1111/bcp.16335","url":null,"abstract":"Current methods of dose determination have contributed to suboptimal and inequitable health outcomes in underrepresented patient populations. The persistent demand to individualise patient treatment, alongside increasing technological feasibility, is leading to a growing adoption of model-informed precision dosing (MIPD) at point of care. Population pharmacokinetic (popPK) modelling is a technique that supports treatment personalisation by characterising drug exposure in diverse patient groups. This publication addresses this important shift in clinical approach, by collating and summarising recommendations from literature. It seeks to provide standardised guidelines on best practices for the development of popPK models and their use in MIPD software tools, ensuring the safeguarding and optimisation of patient outcomes. Moreover, it consolidates guidance from key regulatory and advisory bodies on MIPD software deployment, as well as technical requirements for electronic health record integration. It also considers the future application and clinical impact of machine learning algorithms in popPK and MIPD. Ultimately, this publication aims to facilitate the incorporation of high-quality precision-dosing solutions into standard clinical workflows, thereby enhancing the effectiveness of individualised dose selection at point of care.","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0