British journal of clinical pharmacology最新文献

{"title":"Sustainable medicines development and use: Challenges and opportunities in the sustainable production of active pharmaceutical ingredients.","authors":"Gary M Noonan, Alex Mullen, Sarah Argoud, Stewart F Owen","doi":"10.1111/bcp.16279","DOIUrl":"https://doi.org/10.1111/bcp.16279","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375096","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":"Physiologically based pharmacokinetic modelling to predict potential drug-drug interactions of dersimelagon (MT-7117).","authors":"Akihito Ogasawara, Koki Kojima, Yukiko Murata, Hidetoshi Shimizu","doi":"10.1111/bcp.16271","DOIUrl":"https://doi.org/10.1111/bcp.16271","url":null,"abstract":"<p><strong>Aims: </strong>Dersimelagon is a novel, investigational, orally administered, selective agonist of the melanocortin-1 receptor that has demonstrated efficacy at increasing symptom-free light exposure and an acceptable safety profile in patients with protoporphyria. A phase 1 drug-drug interaction (DDI) study demonstrated that dersimelagon 300 mg has the potential for clinically relevant DDIs with drugs that are substrates for breast cancer resistance protein, such as atorvastatin and rosuvastatin. This study uses physiologically based pharmacokinetic (PBPK) modelling to further investigate the DDI effects at lower doses of dersimelagon with substrate drugs.</p><p><strong>Methods: </strong>The data from in silico, in vitro and in vivo studies were used to construct a PBPK model for dersimelagon to assess the DDI potential between dersimelagon and substrate drugs for cytochrome P450 3A, P-glycoprotein, organic anion transporting polypeptide 1B1/1B3, organic anion transporter 3 and breast cancer resistance protein, including atorvastatin and rosuvastatin.</p><p><strong>Results: </strong>The systemic exposure of atorvastatin based on the maximum plasma concentration and area under the plasma concentration-time curve was predicted to increase 1.21-fold and 1.25-fold, respectively, if coadministered with dersimelagon 100 mg, and 1.42-fold and 1.45-fold with dersimelagon 200 mg. The systemic exposure of rosuvastatin followed trends similar to atorvastatin (1.67-fold and 1.34-fold increase in maximum plasma concentration and area under the plasma concentration-time curve, respectively, with dersimelagon 100 mg, and 2.40-fold and 1.69-fold with dersimelagon 200 mg).</p><p><strong>Conclusion: </strong>Overall, PBPK modelling results indicate that the simulated changes in plasma exposure of atorvastatin and rosuvastatin following coadministration with dersimelagon 100 or 200 mg are not clinically significant, but caution and appropriate clinical monitoring should be recommended.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375095","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":"Economic burden of hospital admissions for adverse drug reactions in France: The IATROSTAT-ECO study.","authors":"Marie-Laure Laroche, Noémie Tarbouriech, Taha Jai, Marie-Blanche Valnet-Rabier, Virginie Nerich","doi":"10.1111/bcp.16266","DOIUrl":"https://doi.org/10.1111/bcp.16266","url":null,"abstract":"<p><strong>Aims: </strong>Hospitalizations for adverse drug reactions (ADR-HA) have increased over the last decade, but the impact of ADR-HA has rarely been evaluated. The aim of this study was to estimate the economic burden of ADR-HA in France.</p><p><strong>Methods: </strong>A partial economic evaluation from the viewpoint of French public health insurance was performed, based on a previous pharmacovigilance study (IATROSTAT) performed in 2018 in public hospital medical units. The cost included direct medical costs, collected retrospectively, from the French hospital discharge database. The economic burden was estimated by calculating the total cost per ADR-HA patient (cost of hospital stays, additional daily cost of specific stays, such as in a resuscitation, intensive care or continuous surveillance unit, drug products and medical devices in addition to Healthcare Resource Group-based tariffs, and specific outpatient consultations and other clinical and technical medical procedures, over 3 months as from the first day of ADR-HA). The robustness of the results was assessed using a one-way deterministic sensitivity analysis of cost factors applying tariffs from 2023 instead of 2018.</p><p><strong>Results: </strong>According to the 2018 tariffs (vs. 2023), the mean total cost per patient with ADR-HA was estimated at €5208 ± €3719 (vs. €5974 ± €4232) ranging from €514 to €23 355 (vs. €618 to €27 380). The total cost for 196 patients with ADR-HA admitted to a sample of French public hospitals was estimated at €1 020 549 (vs. €1 170 960). It could be estimated at €1.3 billion at the national level.</p><p><strong>Conclusions: </strong>In addition to the increase in the number of expensive drugs, the ageing population and polypharmacy, the economic impact of serious ADR-HA weighs heavily on healthcare spending.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371037","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":"Colchicine effect on biomarkers of cardiac remodelling and atherosclerosis in ST-elevation myocardial infarction: A randomized controlled trial.","authors":"Hanan Ahmed Hassanain, Lamia Mohamed El Wakeel, Hazem Khorshid, Marwa Adel Ahmed","doi":"10.1111/bcp.16270","DOIUrl":"https://doi.org/10.1111/bcp.16270","url":null,"abstract":"<p><strong>Aims: </strong>Owing to its underlying inflammatory nature, atherosclerotic cardiovascular disease remains the leading global cause of mortality, particularly post-ST-elevation myocardial infarction (STEMI), a condition with significant risk for further cardiovascular events and mortality. This study aimed to investigate colchicine's effect on inflammation, cardiac remodelling and atherosclerotic risk in STEMI patients.</p><p><strong>Methods: </strong>We conducted a randomized controlled study on 88 STEMI patients undergoing percutaneous coronary intervention. Eligible patients were randomly assigned to 1 of 2 groups. The control group received the guideline-directed medical therapy for STEMI, and the test group received guideline-directed medical therapy and 0.5 mg colchicine twice daily for 3 months. The soluble suppressor of tumorigenicity (sST2), interleukin-1β, lipid profile parameters, triglyceride (TG)/high-density lipoprotein (HDL-C) ratio levels and left ventricular ejection fraction were evaluated for patients at baseline and the end of the 3 months.</p><p><strong>Results: </strong>No significant effects were reported for colchicine on sST2, interleukin-1β levels or left ventricular ejection fraction. Colchicine significantly lowered TG levels vs. controls, 134 (46-353) vs. 176 (72-825) respectively, P = .02, as well as TG/HDL-C ratio levels, 4.16 (2.75-5.24) vs. 5.11 (3.51-8.33),` respectively, P = .024. sST2 levels of the studied cohort were positively correlated with their TG/HDL-C ratio levels (R = .459, P < .001) at the end of follow-up.</p><p><strong>Conclusion: </strong>Our study highlights a promising impact of colchicine on atherosclerosis and cardiac remodelling factors in STEMI patients. Colchicine significantly reduced TG levels and TG/HDL-C ratio and was safe and well tolerated. Larger long-term studies powered to assess clinical outcomes of remodelling are necessary to confirm its beneficial effects in STEMI.</p><p><strong>Clinicaltrial: </strong></p><p><strong>Gov registration id: </strong>NCT06054100.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364462","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":"Evaluating the capability of ChatGPT in predicting drug-drug interactions: Real-world evidence using hospitalized patient data.","authors":"Ramya Padmavathy Radha Krishnan, Euniss Hinyo Hung, Megan Ashford, Clark Ethan Edillo, Charlise Gardner, Hector Blake Hatrick, Byungjun Kim, Angel Wing Yan Lai, Xinran Li, Yvonne Xinyi Zhao, Jacques Eugene Raubenheimer","doi":"10.1111/bcp.16275","DOIUrl":"https://doi.org/10.1111/bcp.16275","url":null,"abstract":"<p><p>Drug-drug interactions (DDIs) present a significant health burden, compounded by clinician time constraints and poor patient health literacy. We assessed the ability of ChatGPT (generative artificial intelligence-based large language model) to predict DDIs in a real-world setting. Demographics, diagnoses and prescribed medicines for 120 hospitalized patients were input through three standardized prompts to ChatGPT version 3.5 and compared against pharmacist DDI evaluation to estimate diagnostic accuracy. Area under receiver operating characteristic and inter-rater reliability (Cohen's and Fleiss' kappa coefficients) were calculated. ChatGPT's responses differed based on prompt wording style, with higher sensitivity for prompts mentioning 'drug interaction'. Confusion matrices displayed low true positive and high true negative rates, and there was minimal agreement between ChatGPT and pharmacists (Cohen's kappa values 0.077-0.143). Low sensitivity values suggest a lack of success in identifying DDIs by ChatGPT, and further development is required before it can reliably assess potential DDIs in real-world scenarios.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364475","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":"Assessment of the influence of body fat indices on antihypertensive drug responses.","authors":"Duygun Altıntaş Aykan, Ahmet Çağrı Aykan, Enes Çelik, Bayram Öztürk","doi":"10.1111/bcp.16265","DOIUrl":"https://doi.org/10.1111/bcp.16265","url":null,"abstract":"<p><strong>Aims: </strong>Less than 50% of patients treated for hypertension reach a target office systolic blood pressure (SBP). We aimed to evaluate the role of adiposity on antihypertensive drug responses in newly diagnosed hypertensive patients.</p><p><strong>Methods: </strong>Estimated glomerular filtration rates, body mass index (BMI), skinfold thickness (SFT), body surface areas and waist circumferences of 150 hypertensive patients naïve to treatment were measured. Treatment protocols were started as combination of angiotensin converting enzyme inhibitor (ACE-I) plus calcium channel blocker (CCB), angiotensin receptor blocker plus CCB or ACE-I plus diuretic. Pre-treatment and change in blood pressure (ΔBP) after 4 weeks treatment were determined. Multiple linear regression analysis was used to find independent predictors of Δblood pressure changes, and multivariable binary logistic regression analysis to find independent predictors of target SBP < 140 mmHg at 4 weeks.</p><p><strong>Results: </strong>A total of 104 patients reached the target systolic pressure of <140 mmHg at 4 weeks. Triceps, mid-abdomen and subscapular SFT were significantly thicker in the uncontrolled blood pressure group (P = .011, P = .006 and P = .016, respectively). Pretreatment SBP (r = 0.644), pretreatment diastolic blood pressure (DBP) (r = 0.188), subscapular SFT (r = -0.318), suprailiac SFT (r = -0.211) and ΔDBP (r = 0.433) were correlated with ΔSBP in correlation analysis. Pretreatment SBP (β = 0.644, 95% CI = 0.697-0.993, P < .001), subscapular SFT (β = -0.253, 95% CI = -0.886--0.329, P < .001), pretreatment DBP (β = -0.380, 95% CI = -0.1001- -0.453, P = .001) and ΔDBP (β = 0.401, 95% CI = 0.377-0.796, P < .001) were independent predictors of ΔSBP in multivariable linear regression analysis. Subscapular SFT was an independent predictor of target SBP < 140 mmHg in multivariable logistic regression analysis (OR = 0.895, 95% CI = 0.832-0.963, P = .003).</p><p><strong>Conclusions: </strong>Subscapular SFT may be a valuable marker for prediction of response to antihypertensive drugs.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341998","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":"Response to: Letter regarding 'Management of serotonin syndrome (toxicity)'.","authors":"Angela L Chiew, Geoffrey K Isbister","doi":"10.1111/bcp.16261","DOIUrl":"https://doi.org/10.1111/bcp.16261","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342006","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":"Cyproheptadine is preferable to benzodiazepines in mild cases of serotonin syndrome (toxicity).","authors":"Michael E Mullins","doi":"10.1111/bcp.16239","DOIUrl":"https://doi.org/10.1111/bcp.16239","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341999","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":"Editorial for the themed issue: Addressing the dual challenges of opioid use disorder and chronic pain in the context of the opioid crisis.","authors":"Mehmet Sofuoglu, R Ross MacLean, Joao P De Aquino","doi":"10.1111/bcp.16273","DOIUrl":"https://doi.org/10.1111/bcp.16273","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342000","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":"Angiotensin-converting enzyme inhibitors attenuate circulating CAF22 and physical decline in congestive heart failure: Diagnostic implications of CAF22.","authors":"Firdos Ahmad, Asima Karim, Javaidullah Khan, Rizwan Qaisar","doi":"10.1111/bcp.16252","DOIUrl":"https://doi.org/10.1111/bcp.16252","url":null,"abstract":"<p><strong>Aims: </strong>Age-associated muscle loss, termed sarcopenia is the major cause of physical disability in patients with congestive heart failure (CHF). Angiotensin-converting enzyme inhibitors (ACEi) are commonly used to treat CHF patients; however, their impacts on the neuromuscular junction (NMJ) and sarcopenia in CHF patients remain poorly understood. We aim to investigate the potential impact of ACEi on NMJ and CHF-induced sarcopenia.</p><p><strong>Methods: </strong>The cardiac function, short physical performance battery, handgrip strength (HGS), appendicular skeletal mass index, gait speed (GS) and plasma c-terminal agrin fragment-22 (CAF22), a marker of NMJ degradation, were assessed in controls (n = 81) and CHF patients treated with (n = 134) or without (n = 145) ACEi.</p><p><strong>Results: </strong>Irrespective of treatment, HGS and GS, indicators of sarcopenia, were profoundly declined in the patients with CHF vs. controls. However, patients on ACEi demonstrated significantly better HGS and GS compared to non-ACEi patients (P < .001). The level of CAF22 was significantly lower (P < .0001) in the ACEi-treated compared to non-ACEi CHF patients. Further, the level of CAF22 was inversely correlated (R² = .33, P < .0001) with HGS in both ACEi and non-ACEi CHF patients, while CAF22 was inversely correlated with GS and short physical performance battery only in ACEi-treated but not in patients on other therapies without ACEi. The receiver operating characteristic curve analysis revealed CAF22 as a potential diagnostic marker (95% confidence interval: 0.785-0.883; P < .0001) for CHF.</p><p><strong>Conclusion: </strong>Collectively, these findings strongly suggest that ACEi limits CHF-induced neuromuscular disjunction and physical disability in CHF. CAF22 has shown diagnostic implications for CHF.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341997","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}