British journal of clinical pharmacology最新文献

{"title":"Exploring the factors associated with difficulties in extracting tablets or capsules from press-through-package sheets","authors":"Masami Tsuchiya,&nbsp;Shungo Imai,&nbsp;Masaki Asano,&nbsp;Yuri Shimizu,&nbsp;Hayato Kizaki,&nbsp;Yukiko Ito,&nbsp;Makoto Tsuchiya,&nbsp;Ryoko Kuriyama,&nbsp;Nao Yoshida,&nbsp;Masanori Shimada,&nbsp;Takanori Sando,&nbsp;Tomo Ishijima,&nbsp;Satoko Hori","doi":"10.1111/bcp.16355","DOIUrl":"10.1111/bcp.16355","url":null,"abstract":"<p>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.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 2","pages":"479-484"},"PeriodicalIF":3.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773092/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Highlights","authors":"","doi":"10.1111/bcp.16348","DOIUrl":"https://doi.org/10.1111/bcp.16348","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"90 12","pages":"2959"},"PeriodicalIF":3.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762674","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}

{"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":"<p><strong>Aims: </strong>Psychedelics, including mescaline, may serve as novel treatments for depression and anxiety. However, data is scarce on the safety of mescaline.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","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}

{"title":"Applying the estimand framework to clinical pharmacology trials with a case study in bioequivalence","authors":"Helle Lynggaard,&nbsp;Sue McKendrick,&nbsp;Mark Baird,&nbsp;Essam Kerwash,&nbsp;Vivian Lanius,&nbsp;Florian Lasch,&nbsp;David Wright","doi":"10.1111/bcp.16347","DOIUrl":"10.1111/bcp.16347","url":null,"abstract":"<p>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 <i>intercurrent events</i>, 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.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 2","pages":"310-324"},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773105/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"<p><strong>Aims: </strong>The present study aimed to quantitatively investigate the potential drug-drug interaction (DDI) mechanism between meropenem (MEPM) and valproic acid (VPA).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (C_max) 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.</p><p><strong>Conclusions: </strong>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.</p>","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}

{"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":"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial registration number: </strong>NCT05673603.</p>","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}

{"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":"<p><p>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.</p>","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}

{"title":"Toxicokinetic modelling of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite in pigs following pulmonary administration.","authors":"Adrian A Doerr, Christiane Dings, Omar Zaher, Frederike Nordmeier, Nadja Walle, Matthias W Laschke, Michael D Menger, Peter H Schmidt, Markus R Meyer, Thorsten Lehr, Nadine Schaefer","doi":"10.1111/bcp.16340","DOIUrl":"https://doi.org/10.1111/bcp.16340","url":null,"abstract":"<p><strong>Aims: </strong>Since their emergence on the drug market, synthetic cannabinoids (SC) are still gaining increasing importance in forensic toxicology. The representatives of the so-called new psychoactive substances have in common that they have not undergone preclinical safety studies. Hence, knowledge on toxicokinetic (TK) data is sparse. As an alternative to human studies not being allowed for ethical reasons, a sophisticated pig model was applied in the present study to assess the TK of the SC 5F-MDMB-P7AICA.</p><p><strong>Methods: </strong>Pigs pulmonarily received 5F-MDMB-P7AICA via an ultrasonic nebulizer. The parent compound and its main metabolite 5F-MDMB-P7AICA dimethyl butanoic acid were determined in serum and whole blood using liquid chromatography-tandem mass spectrometry. Obtained data was analysed by population (pop) TK modelling. The final pop TK model parameters for pigs were upscaled via allometric scaling techniques for the prediction of human exposure.</p><p><strong>Results: </strong>The serum concentration-time profiles of the parent and the pop TK analysis revealed that a 4-compartment model best describes the TK data. The administration of the aerosol into the lung compartment follows zero-order kinetics. A transit compartment was further included to accurately describe the time delay between detection of the parent and the metabolite. Despite the different structure, TK parameters were found to be comparable to other examined SC.</p><p><strong>Conclusion: </strong>The predictions of human SC exposure suggest that multiple administration of 5F-MDMB-P7AICA substantially enhances the window of detection. The simulations pose extrapolation of the data used for model development with respect to dose linearity and allometric scaling to humans.</p>","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":"142680798","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}

{"title":"Determination of the optimal obesity-adjusted dosing weight for enoxaparin.","authors":"Gregory W Roberts, Viviane De Menezes Caceres, Anthony Damiani, Nicholas Scarfo, Desmond B Williams, Patrick T Russell","doi":"10.1111/bcp.16338","DOIUrl":"https://doi.org/10.1111/bcp.16338","url":null,"abstract":"<p><strong>Aims: </strong>The ideal dosing weight metric for enoxaparin remains elusive. Dosing remains focused on actual body weight, which may inadvertently increase the risk of bleeding in those with obesity, or ideal weight, which may underdose those with obesity. Our aim was to determine the optimal obesity-adjusted enoxaparin dosing weight.</p><p><strong>Methods: </strong>Multisite retrospective data were collected over a 2.0-year period for those with minimum 48 h of in-hospital twice-daily enoxaparin and factor anti-Xa level 3-5 h postdose (n = 220). Multiple linear regression calculated the associated variance between a range of nominal dosing weights and factor anti-Xa levels, adjusted for renal function. Dosing weights were calculated as ideal body weight (IBW) and then adjusted for increasing percentages of weight above IBW, i.e. IBW + 10% above IBW, IBW + 20% etc. up to actual body weight. A similar approach was used for lean body weight (LBW).</p><p><strong>Results: </strong>For body mass index ≥30 kg/m² optimal variance explained by dosing weight metrics was at IBW + 40% (23%) and similarly for LBW + 40% (23%). Using actual body weight (ABW) had lowest associated variance with factor anti-Xa levels (18%) followed by unadjusted IBW (13%) or unadjusted LBW (19%). In those with body mass index <30 kg/m² there was similar associated variance in the ranges of IBW + 20-50% and LBW 10-40% (21%).</p><p><strong>Conclusion: </strong>Compared to IBW + 40% or LBW + 40% use of ABW to calculate dose was poorly associated with factor anti-Xa levels, as was IBW or LBW. IBW + 40% and LBW + 40% require further study as a dosing weight metric and may provide a more consistent factor anti-Xa response in those with obesity.</p>","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":"142680775","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}

{"title":"Risk factors for lenvatinib-induced hypertension in patients with hepatocellular carcinoma: A retrospective study","authors":"Shusuke Uekusa,&nbsp;Misaki Nakashin,&nbsp;Yuki Hanai,&nbsp;Maho Nemoto,&nbsp;Sachiko Yanagino,&nbsp;Yoshiki Arita,&nbsp;Takahiro Matsumoto,&nbsp;Noritaka Wakui,&nbsp;Hidenari Nagai,&nbsp;Koji Higai,&nbsp;Kazuhiro Matsuo","doi":"10.1111/bcp.16337","DOIUrl":"10.1111/bcp.16337","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). LEN therapy for HCC is associated with a high incidence of adverse events, including hypertension (HTN). However, the risk factors associated with LEN therapy remain unclear. This study investigated the incidence of LEN-induced HTN (LENiHTN), and the relationship between HTN incidence and patient demographics in patients with HCC receiving LEN therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a single-centre, retrospective study of patients with HCC who received LEN therapy between 19 April 2018 and 30 September 2020. The observation period was from 1 week before the start to 1 month after the end of LEN administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-five patients with HCC were enrolled. Any grade LENiHTN was found in 74.7% of patients. Among patients with LENiHTN, the use of 2 or more antihypertensive agents before starting LEN was less common (<i>P</i> = .007); serum potassium (K) and albumin–bilirubin score (ALBI) were lower (<i>P</i> = .013 and 0.038, respectively); and albumin (Alb) was higher (<i>P</i> = .025). The cut-off values of K, Alb and ALBI for HTN were estimated at 4.1 mEq L⁻¹, 3.1 g dL⁻¹ and −1.736, respectively. In the multivariable analysis, low K (adjusted HR: 2.078) and low ALBI (adjusted HR: 2.845) were independent risk factors for LENiHTN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Low K, high Alb and low ALBI were independent risk factors for LENiHTN. Systematic evaluation of HTN risk and early intervention for HTN prevention among high-risk patients can markedly enhance LEN therapy efficacy and use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"894-902"},"PeriodicalIF":3.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}