British journal of clinical pharmacology最新文献

{"title":"Population modelling of nilotinib exposure vs. longitudinal BCR::ABL1 response in patients with chronic phase chronic myeloid leukaemia using a semimechanistic disease model","authors":"Sherwin K. B. Sy,&nbsp;Deok Yong Yoon,&nbsp;Christelle Darstein,&nbsp;Yiqun Yang,&nbsp;Kohinoor Dasgupta,&nbsp;Shruti Kapoor,&nbsp;Matthias Hoch,&nbsp;Kai Grosch","doi":"10.1111/bcp.16381","DOIUrl":"10.1111/bcp.16381","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to evaluate the exposure–efficacy relationship of nilotinib and longitudinal BCR::ABL1 levels in patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukaemia in chronic phase (CML-CP) and those who are imatinib-resistant or intolerant using a semimechanistic disease model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The analysis included 489 CML-CP patients from 3 nilotinib trials (NCT00109707; NCT00471497; NCT01043874) with duration of follow-up ranging from 2 to 9 years. The semimechanistic disease model of CML-CP consisted of quiescent leukaemic stem cells, proliferating drug-susceptible and -resistant bone marrow cells. Drug effect on the elimination of susceptible cells was characterized by a maximum response model based on the individual daily area under the concentration–time curve over the last 24 h simulated using their empirical Bayes estimates from a population pharmacokinetic model. The influence of line of therapy was evaluated on model parameters and its impact was investigated through simulations of the major molecular response (MMR) rate, defined as the proportion of the simulated profiles that achieved BCR::ABL1 level of ≤0.1% at 48 and 96 weeks of treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The final disease model was based on a truncated 3-year data that characterized the biphasic pattern of BCR::ABL1 transcript profiles. Line of therapy was a significant covariate of the drug kill effect, susceptible and resistant cells. Simulations of BCR::ABL1 time course predicted MMR rates at 48 weeks and 96 weeks for both nilotinib 300 and 400 mg twice-daily of 66–71 and 77–82% in first-line, and 34–39 and 46–54% in second-line, respectively. Results are consistent with observed MMR rates in the respective trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The ability to distinguish molecular response between lines of therapy is demonstrated using model-based analysis. These nilotinib information enable the extrapolation of novel tyrosine kinase inhibitors (e.g., asciminib) response to other lines of therapy in patients with CML-CP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 5","pages":"1419-1430"},"PeriodicalIF":3.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909313","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":"Medication review interventions for adults living with advanced chronic kidney disease: A scoping review","authors":"Cathy Margaret Pogson,&nbsp;Rosalynn Austin,&nbsp;Jignesh Prakash Patel,&nbsp;David Collins Wheeler","doi":"10.1111/bcp.16363","DOIUrl":"10.1111/bcp.16363","url":null,"abstract":"<p>Structured medication reviews (SMRs) were introduced into the National Health Service (NHS) Primary Care to support the delivery of the NHS Long-Term Plan for medicines optimization. SMRs improve the quality of care, reduce harm and offer value for money. However, evidence to support SMRs for patients with chronic kidney disease (CKD) stage G4-5D with elevated risk of cardiovascular disease and premature mortality is unknown. This scoping review aimed to assess the extent and nature of SMR research in the population of patients with CKD stage G4-5D. Electronic databases were searched on 20 October 2023. Studies were eligible if they described an SMR in adults with CKD stage G4-5D, regardless of the study design. Data detailing the global patterns, population and intervention descriptions, professionals performing SMR, and reported areas for future research were extracted. The extracted outcome data were categorized as clinical, patient-important, medication-related and experience-related. A narrative synthesis was completed. Seventeen studies (81%) were conducted in nephrology outpatient settings, three (14%) during acute hospital admissions and one (5%) within the community pharmacy. Eighteen studies (86%) were quantitative, including five randomized controlled trials. Ten (48%) studies were undertaken in the United States and Canada, and two in Europe (France and Norway). No such studies have been conducted in the United Kingdom. Our review revealed that there is a lack of evidence for SMR as a strategy to reduce polypharmacy and harms from medication for adults with CKD stage G4-5D. Therefore, further research is required in this area.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 4","pages":"1132-1156"},"PeriodicalIF":3.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16363","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909311","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":"Therapeutic drug monitoring-Does it really matter?","authors":"Hans Lennernäs, Jack Cook, Dennis A Hesselink","doi":"10.1111/bcp.16387","DOIUrl":"https://doi.org/10.1111/bcp.16387","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909325","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":"Medication adherence—Everybody's problem but nobody's responsibility?","authors":"Amy Hai Yan Chan,&nbsp;Daniel Frank Broughton Wright","doi":"10.1111/bcp.16384","DOIUrl":"10.1111/bcp.16384","url":null,"abstract":"&lt;p&gt;Medication nonadherence has become somewhat of an adage—starting with Hippocrates commonly used quote by adherence researchers: ‘&lt;i&gt;Keep a watch … on the faults of the patients, which often make them lie about the taking of things prescribed&lt;/i&gt;’. Many publications focused on adherence refer to the statistic where approximately 50% of medicines prescribed to people with long-term conditions are not taken as recommended. This number originated in a Cochrane review published in 2002&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and reached a global audience in the 2003 World Health Organization ‘Adherence to Long-Term Therapies: Evidence for Action’.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Whilst these documents are well overdue for updates, the statistic they promote is hardly groundbreaking anymore and has almost become accepted in practice and research as the ‘norm’. Despite decades of referring to the same statistic and millions of dollars of funding dedicated to research to investigate nonadherence, there has been little shift in the size and nature of the problem.&lt;/p&gt;&lt;p&gt;It is therefore time to ask ourselves—as clinicians, researchers and policymakers—whether we are becoming complacent in accepting that nonadherence is a public health problem that is here to stay. Medication adherence seems to be a problem that affects everybody—regardless of age, ethnicity, gender or health, yet nobody's responsibility to address. Is adherence simply a health problem that cannot be solved or have the key actors, such as health professionals and policymakers, become complacent?&lt;/p&gt;&lt;p&gt;The recent paper ‘&lt;i&gt;Pan-European survey on medication adherence management by healthcare professionals&lt;/i&gt;’ by Kamusheva and colleagues&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; as part of the European Cooperation in Science and Technology (COST) project ENABLE (European Network to Advance Best Practices and Technology on Medication AdherencE) comes at a timely moment as the adherence field begins to show signs of clinical inertia. The study provides insights into the practice of health professionals in relation to medication adherence across 40 European countries in a range of health professionals. The findings outline a sobering outlook on the current landscape of medication adherence practice. The survey data show that there is a risk that medication adherence is being de-prioritized in healthcare delivery despite being a critical determinant of variability in medication response and a central driver of good health outcomes.&lt;/p&gt;&lt;p&gt;Of the 2875 health professionals who participated, the most used method for monitoring medication adherence was by far ‘asking the patient’ (86.4% of respondents). Checking dispensing history or prescriptions was only performed by just over half of respondents (56.8%) despite the relatively easy accessibility to health records to health professionals. This is concerning and surprising as other aspects of clinical decision-making, such as the diagnosis of a health condition or medication administrati","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"681-683"},"PeriodicalIF":3.1,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902574","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":"Clinical relevance of immune checkpoint inhibitors for the analgesic effect of opioids: A retrospective propensity score analysis","authors":"Takahiro Sumimoto,&nbsp;Ryota Tanaka,&nbsp;Yuko Murakami,&nbsp;Ryosuke Tatsuta,&nbsp;Hiroki Itoh","doi":"10.1111/bcp.16377","DOIUrl":"https://doi.org/10.1111/bcp.16377","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to determine the clinical relevance of the influence of coadministration of immune checkpoint inhibitors (ICIs) on the analgesic effects of opioids, focusing on the amount of change in opioid dosage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study used data from patients who used opioids during anticancer therapy at the Oita University Hospital between September 2014 and October 2023. The primary outcome measure was the amount of change in morphine mg equivalent opioid dose during the period of anticancer therapy. Propensity score matching was performed to reduce confounding effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study enrolled 235 patients; 101 received ICI and 134 received no ICI. Before propensity score matching, there were significant differences between the ICI and non-ICI groups in lines of anticancer therapy, type of primary cancer, body mass index, maximum opioid dose and the amount of change in opioid dose. Following propensity score matching, 73 patients each were included in the ICI and non-ICI groups. Analysis of the propensity score-matched cohort showed a significant increase in the median amount of change in opioid dose in ICI group <i>vs</i> non-ICI group (22.5 <i>vs</i>. 15.0 morphine mg equivalents, interquartile range; 0.0, 40.0 <i>vs</i>. 0.0, 30.0, <i>P</i> = .044). Multiple regression analysis identified ICI administration and body mass index as significant independent factors associated with the amount of change in opioid dose (<i>P</i> = .014 and .027, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ICI administration significantly increased opioid dosage regardless of patient background. Our findings would provide valuable insight into future pain management strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 5","pages":"1409-1418"},"PeriodicalIF":3.1,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880052","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":"Low-dose amitriptyline: A potential therapeutic option for chronic pain in older people","authors":"Takayuki Suga,&nbsp;Trang Thi Huyen Tu,&nbsp;Motoko Watanabe,&nbsp;Takahiko Nagamine,&nbsp;Akira Toyofuku","doi":"10.1111/bcp.16380","DOIUrl":"10.1111/bcp.16380","url":null,"abstract":"&lt;p&gt;The use of antidepressants in older adults with chronic pain is controversial. We found Dr. Narayan et al.'s article, titled ‘Efficacy and Safety of Antidepressants for Pain in Older Adults: A Systematic Review and Meta-Analysis’, on the use of antidepressants in older people with chronic pain to be highly engaging.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; They conducted a systematic review and meta-analysis on the efficacy and safety of antidepressants for chronic pain in older people. Due to various limitations, they concluded that the benefits and harms of antidepressant medicines for most types of chronic pain, especially knee OA, are unclear.&lt;/p&gt;&lt;p&gt;BMS, a common type of chronic orofacial pain affecting mainly postmenopausal women, has uncertain pathophysiology.&lt;/p&gt;&lt;p&gt;We previously reported that low doses of amitriptyline are effective in managing pain in older people with BMS.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Furthermore, even in patients over 80 years old, amitriptyline demonstrates efficacy when used in low doses with careful administration.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Regarding common side effects, managing these side effects in elderly patients will be effective through regular visits and examination.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; Hence, it is crucial to monitor for anticholinergic side effects such as drowsiness, dry mouth and constipation, as well as potential falls due to dizziness and any changes in cognitive function in clinical assessment.&lt;/p&gt;&lt;p&gt;A therapeutic window exists for the dosages of amitriptyline that are effective in managing chronic pain, indicating that its efficacy is not dose-dependent.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; In contrast to the doses used in psychiatry for depression (typically 100 mg/day or more), amitriptyline is effective at doses of 5–20 mg/day in the treatment of BMS. The use of amitriptyline at this dosage is considerably lower than the doses employed in the RCTs included in the authors' study, suggesting a reduced risk of side effects and withdrawal symptoms.&lt;/p&gt;&lt;p&gt;The challenges of administering antidepressants to older people with chronic pain are not only limited to concerns about side effects but also encompass issues related to their overall efficacy in this population. Serotonin's role in pain modulation is complex, as it can either exacerbate or alleviate pain depending on the receptor subtype activated. This bidirectional effect is attributed to the distinct pathways involved in serotonin-mediated pain processing, with some receptors promoting analgesia and others enhancing nociception.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Additionally, the elevation of serotonin levels might disrupt the delicate equilibrium with dopamine, thus hindering pain inhibition via the reward pathway. Therefore, increasing serotonin levels alone may exacerbate pain rather than produce therapeutic benefits.&lt;/p&gt;&lt;p&gt;Moreover, chronic pain modulation involves not only serotonin but also other monoamines, such as dopamine and noradrenaline. Consequently, antidepr","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"921-922"},"PeriodicalIF":3.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881386","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":"Antidotes in the management of poisoned patients: What have we gained over the last decade?","authors":"David Michael Wood,&nbsp;James William Dear,&nbsp;Ruben Thanacoody,&nbsp;David Nelson Juurlink,&nbsp;Angela Lin Chiew,&nbsp;Paul Ivor Dargan","doi":"10.1111/bcp.16353","DOIUrl":"10.1111/bcp.16353","url":null,"abstract":"&lt;p&gt;Poisoning remains an extremely common medical issue worldwide, with just over 71 000 poisoning-related admissions to hospitals in England in the 2023/24 financial year&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and a global age-standardized death rate from poisoning of 0.7 per 100 000 people in 2021.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The management of poisoning frequently involves decontamination (to reduce absorption/exposure to the poison), close observation to identify clinical deterioration and, where appropriate, consideration of antidote therapy to attenuate the effects of the poison. As a result, antidotes remain commonly used in the emergency management of the poisoned patient. The Toxicology Investigators Consortium (ToxIC) reported that 41% of 7392 poisoned patients who had a bedside consult by a medical toxicologist in the United States in 2023 were treated with one or more antidotes; the most commonly used antidotes (defined as being administered to more than 10% of patients) were thiamine, folate, acetylcysteine and naloxone.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In 2016, the British Journal of Clinical Pharmacology published a themed issue reviewing the evidence for the use of various antidotes in gut decontamination, the management of specific poison-related clinical complications (e.g., ECG QT prolongation, seizures), the use of specific antidotes (e.g., flumazenil, naloxone, acetylcysteine) and the management of specific drug-related poisonings (such as poisonings involving calcium channel blockers, beta-blockers, organophosphates, digoxin, insulin, sulfonylureas and toxic alcohols). The themed issue included two accompanying editorials discussing the challenges around the use of antidotes and the limited evidence for their effectiveness and safety.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; It was noted that &lt;i&gt;‘there are dozens of antidotes used for hundreds of potential toxins, but only a few are used regularly&lt;/i&gt;’, and also that the most commonly-used antidotes included ‘&lt;i&gt;activated charcoal, acetylcysteine, naloxone, sodium bicarbonate, atropine, flumazenil, therapeutic antibodies and various vitamins&lt;/i&gt;’.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Based on the challenges and lack of evidence, clinicians should seek input of specialized toxicological advice from poisons centres and information services when using antidotes, particularly those that are rarely used or that the clinician is unfamiliar with.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Since the 2016 British Journal of Clinical Pharmacology antidote-themed issue, there have been changes, as summarized in the review by Gosselin et al., in how toxicologists view the role of gut decontamination in the management of poisoned patients.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Additionally, several new drugs and drug classes have been developed and licensed for therapeutic use. As these become more widely used, there is an increased risk of accidental or intentional poisoning from them. In some instances, novel antidotes have been developed to manage the un","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"593-594"},"PeriodicalIF":3.1,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16353","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876165","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":"Killing several birds with one stone: A multi-indication population pharmacokinetic model and Bayesian estimator for enteric-coated mycophenolate sodium","authors":"Yeleen Fromage,&nbsp;Hamza Sayadi,&nbsp;Kevin Koloskoff,&nbsp;Pierre Marquet,&nbsp;Marc Labriffe,&nbsp;Caroline Monchaud,&nbsp;Jean-Baptiste Woillard","doi":"10.1111/bcp.16374","DOIUrl":"10.1111/bcp.16374","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Mycophenolic acid (MPA), the active component of enteric-coated mycophenolate sodium (EC-MPS), exhibits highly variable pharmacokinetics. Only a few population pharmacokinetic (popPK) models and Bayesian estimators (MAP-BE) exist for estimating MPA AUC and all in renal transplantation. This study aimed to develop a popPK model and MAP-BE for MPA AUC estimation using a limited sampling strategy (LSS) in solid organ transplant (SOT), haematopoietic stem cell (HSC) recipients and patients with autoimmune diseases (AID) on EC-MPS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Full and sparse MPA pharmacokinetic profiles were extracted from our ISBA system, split into development (75%) and validation (25%) sets. An additional extraction was performed after the modelling process for external validation. Pharmacokinetic parameters were estimated using Monolix® (SAEM algorithm). Several absorption models (first order, transit, gamma) were compared. AUC_predicted by MAP-BE and LSS was compared to the all-sample MAP-BE AUC_reference using Simulx®.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 153 PK profiles (863 concentration) from 129 patients (116 SOT and HSC, 13 AID), median [min–max] age 45 years [6–80]. A one-compartment model with double-gamma absorption and first-order elimination best fitted the data. The final model included the EC-MPS indication and inter-occasion variability on gamma rate constants. Main PK parameters (mean ± SD) were Cl/F = 4.99 ± 2.22 L/h and Vd/F = 12.60 ± 0.08 L. The optimal LSS at 20 min, 2 h and 4 h post-dose showed good performance in both validation sets (rMPE −2.67% and −4.91%; RMSE 13.55% and 13.47%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The double-gamma absorption model provided an accurate fit. The MAP-BE offers a tool for EC-MPS dose individualization in SOT, HSC and AID patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 5","pages":"1396-1408"},"PeriodicalIF":3.1,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876168","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":"Implementability of opioid deprescribing interventions at transitions of care: A scoping review","authors":"Jeffery Wang,&nbsp;Carl R. Schneider,&nbsp;Aili V. Langford,&nbsp;Mouna Sawan,&nbsp;Chung-Wei Christine Lin,&nbsp;Antonius Nugraha Widhi Pratama,&nbsp;Danijela Gnjidic","doi":"10.1111/bcp.16369","DOIUrl":"10.1111/bcp.16369","url":null,"abstract":"<p>Continuation of opioids at transitions of care increases the risk of long-term opioid use and related harm. To our knowledge, no study has examined the implementability of opioid deprescribing interventions at transitions of care. Our scoping review aimed to identify the type of opioid deprescribing interventions employed at transitions of care and assess the implementability of tested interventions. Nine electronic databases were searched on 15 May 2023 for English-language studies of adults transitioning between care settings, where opioid deprescribing interventions targeting patients, clinicians or health systems were implemented. Implementability was assessed using the Cochrane Intervention Complexity Assessment Tool for Systematic Reviews to determine intervention complexity, and mapped to the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to understand the process evaluation. A total of 79 studies were identified, with 94.0% (<i>n =</i> 74) examining hospital-to-home transitions. Mixed interventions (combination of pharmacological and nonpharmacological) were tested in 49.0% (<i>n =</i> 39) of studies. Pharmacological interventions were identified in 31.0% (<i>n =</i> 24) of studies, and the remaining 20.0% (<i>n =</i> 16) applied nonpharmacological interventions. Mixed interventions comprising multiple components were the most complex and resulted in reduced opioid use across transitions of care in 28.0% (<i>n =</i> 22) of studies. Few studies reported on RE-AIM dimensions including implementation (5.0% of studies), reach (4.0%), adoption (4.0%) and maintenance (0%). Most opioid deprescribing interventions targeted hospital to home care transition with mixed results in opioid deprescribing. Further research should consider the implementability of interventions during transitions of care to elucidate the impact of opioid deprescribing interventions across care settings.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"698-728"},"PeriodicalIF":3.1,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876166","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":"Strategies employed and experiences associated with the implementation of pharmaceutical services and interventions in geriatric wards: A scoping review","authors":"Alan Maicon de Oliveira,&nbsp;João Paulo Vilela Rodrigues,&nbsp;Isabella do Vale de Souza,&nbsp;Thalita Zago Oliveira,&nbsp;Márcia dos Santos,&nbsp;Fabiana Rossi Varallo,&nbsp;Leonardo Régis Leira Pereira","doi":"10.1111/bcp.16373","DOIUrl":"10.1111/bcp.16373","url":null,"abstract":"<p>Evidence indicates a lack of clarity regarding the contributions of interventions aimed at optimizing pharmacotherapy, primarily guided by pharmaceutical care, for clinically significant improvements in older individuals. Thus, there is a need to deepen the understanding of this scenario and the factors involved. Therefore, this study aims to map and summarize scientific evidence regarding experiences and strategies employed in providing pharmaceutical services and interventions in geriatric wards. A scoping review was conducted based on 3 electronic databases (PubMed, EMBASE and Web of Science). Studies meeting the inclusion criteria, published up to September 2024, and in English, Spanish or Portuguese were selected. Experimental and observational studies were eligible for inclusion. Screening, eligibility, extraction and assessment of the studies were carried out by 2 independent researchers. The exploration of bibliographic databases yielded 3,976 references, and 40 studies were deemed suitable for inclusion. Predominantly conducted in countries with high human development, these studies categorized services and interventions as: (i) medication review; (ii) medication reconciliation; and (iii) pharmaceutical counselling. Highlighted tools included STOPP and START criteria, Beers criteria, and the Medication Appropriateness Index, facilitating identification of issues such as potentially inappropriate medications (27.6–90.8% of older individuals using at least 1 potentially inappropriate medication), drug-related problems (34.5–98.2% of patients with at least 1 drug-related problem) and adverse drug events (58–88.4% of patients with at least 1 adverse drug event). The acceptance rate of interventions exhibited considerable variation (13–95.3%). Only 10 studies evaluated clinical outcomes in patients. Barriers included the need for additional training for pharmacists in geriatrics, significant time investment, lack of continuity in assessments and a lack of recognition of interventions by other members of the multiprofessional team. There is a clear trend towards improving medication prescription adequacy and contributing to the quality of pharmacotherapy through pharmaceutical services and interventions in geriatric wards. However, several gaps still need to be addressed, and this review emphasizes identifying obstacles to be overcome, providing guidance for future investigations.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 3","pages":"729-739"},"PeriodicalIF":3.1,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876170","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}