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A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English‐language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease‐modifying" effects. A more‐refined terminology to describe precisely these actions needs to be developed. [ABSTRACT FROM AUTHOR]

Objective: Although Ireland has one of the highest levels of well‐being in Europe, having a health condition has been found to have a direct negative impact. The aim of this study is to evaluate the current situation and the experiences of patients with epidermolysis bullosa (EB), a rare genetic skin disease, and their relatives living in Ireland, with a focus on burdens and helpful practices. Methods and Measures: In a mixed‐methods design, a series of standardised questionnaires were combined with open‐ended questions. Via an online survey, data from n = 59 EB patients and relatives of EB patients living in Ireland were collected. Results: EB affects both the patients and their relatives. Burdens were found in relation to the visibility of EB, the degree of severity, the current health status, reduced mobility, the financial impact of EB, the psychosocial impact and personal and social resources. The paper also analyses existing resources and highlights opportunities for support and needs of improvement. Conclusion: Quality of life with EB is influenced by somatic symptoms and the psychosocial burden. Individual helpful practices in dealing with this rare disease can be considered as mediators, but they need to be supported by structural and healthcare improvements. Patient or Public Contribution: The perspective of EB patients, their relatives and EB experts were taken into account in the development of the study design via two feedback loops with the EB patient organisations DEBRA Ireland and DEBRA Austria. The design was adapted accordingly. Additionally, by including open‐ended questions, patients and relatives could contribute their individual perspectives and add insights into their lives with EB that might not have been captured with the structured online survey alone. [ABSTRACT FROM AUTHOR]

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient‐centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography‐mass spectrometry (LC–MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient‐centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy. [ABSTRACT FROM AUTHOR]

The progress the Internet has experienced in recent years has brought about huge changes and social transformation in all aspects of our lives. One such aspect greatly impacted has been our health, where we can talk about the existence of an ‘Internet of Medical Things’. Amid this digital drift, we have seen the development of pharmaceutical drugs that provide information to patients and their attending healthcare teams concerning medication, doses ingested, and time of ingestion. These are digital pills or digital medication. In this context, the purpose of my paper is to analyze the ethical and legal impact of digital medication, further analyzing the implications concerning the right of service users to make decisions over their own health in Spain. [ABSTRACT FROM AUTHOR]

The national quality framework (NQF) has been implemented to improve the safety and quality of alcohol and other drug (AOD) treatment and provide a nationally consistent approach to treatment quality in Australia. At the same time, concerns have been raised that, in the absence of appropriate regulatory structures to support the NQF, the quality and safety of AOD treatment services cannot be guaranteed in Australia. An effective enforcement strategy is critical to the ability of the NQF to provide a nationally consistent approach to the delivery of AOD treatment in Australia. The monitoring and enforcement strategy proposed by the NQF encompasses two different mechanisms. For specialist AOD treatment providers in receipt of government funding, monitoring and enforcement of the NQF will occur via contractual arrangements. For providers not in receipt of government funding, monitoring and enforcement will be managed by regulatory mechanisms as decided by each jurisdiction. This proposed enforcement strategy raises the question of whether contractual arrangements are the most effective mechanism for monitoring and enforcing the NQF in publicly funded specialist AOD treatment providers. This paper considers whether a licensing regime may address the shortcomings that arise from the proposed strategy. It argues that the pluralistic approach to the monitoring and enforcement of the NQF will result in substantive differences in how the NQF is enforced both within individual jurisdictions and on a broader national level. A licensing regime, therefore, would be a more appropriate monitoring and enforcement strategy. [ABSTRACT FROM AUTHOR]

The public health sector, considered to be vital, especially in this pandemic crisis of COVID‐19, requires automation and control of drug distribution in pharmacies commonly called: "Dispensing." In this paper, we address the medication assignment problem for automated dispensing cabinets (ADCs). First, we use a network of conflicting timed event graphs (CTEGs), a class of timed Petri nets with shared resources, to model pharmaceutical cabinets. Second, we develop a new method for controlling CTEGs under mutual exclusion constraints (MECs) to solve the problem of drug assignment, using a control approach based on Min‐Plus algebra. Finally, a case study of assigning drugs is given to illustrate the proposed methodology and show the efficiency of the developed control laws. [ABSTRACT FROM AUTHOR]

Aims: To systematically review the literature investigating the links between stigma and the management of type 1 diabetes. Methods: A systematic literature review was conducted in accordance with PRISMA guidelines. Both quantitative and qualitative data were considered. Included papers were subject to quality assessment using the Mixed Methods Appraisal Tool (MMAT), and a narrative synthesis of results was reported. Results: Nineteen articles met the inclusion criteria and were included in the final analysis. Amongst these, one study used mixed methods, nine were qualitative, and nine were quantitative. All studies found a negative relationship between stigma and type 1 diabetes management. Qualitative studies provided a further understanding of the effects observed in the quantitative studies and found that stigma can affect self‐care activities, disclosure of diabetes, and the uptake of diabetes technology. Systemic causes of stigma and intersectional stigma were also observed. Conclusions: This review highlights that people with type 1 diabetes are negatively affected by stigma, irrespective of their age, gender, culture, or use of diabetes technology. Quantitative studies were limited, in that all studies were cross‐sectional, and there was a lack of standardisation across outcome measures. There is a need for interventions to target stigma on both an individual and a systemic level, particularly where people experience multiple intersecting stigmas. [ABSTRACT FROM AUTHOR]

Depression is a serious public health problem, and adolescence is an 'age of risk' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico‐amygdala circuit, lowers sensitivity to rewards in the cortico‐striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self‐medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress‐related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a 'next generation' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents. [ABSTRACT FROM AUTHOR]

The article comments on the paper by B. Pardo and colleagues about the production of methamphetamine in Afghanistan. Topics discussed include the role of ephedra in the expansion of methamphetamine production in the country, the uncertainty of the Taliban's ban on drug production, and the possible increase in the manufacture of methamphetamine or other synthetic substances using synthetic precursors.

Aims: A key reason for the failure of antituberculosis (anti‐TB) treatment is missed doses (instances where medication is not taken). Adverse drug reactions (ADRs) are 1 cause of missed doses, but the global evidence, their relative contribution to missed doses vs. other causes, the patterns of missed doses due to ADRs and the specific ADRs associated with missed doses have not been appraised. We sought to address these questions through a scoping review. Methods: MEDLINE, Embase and Web of Science were searched on 3 November 2021 using terms around active TB, missed doses and treatment challenges. Studies reporting both ADR and missed dose data were examined (PROSPERO: CRD42022295209). Results: Searches identified 108 eligible studies: 88/108 (81%) studies associated ADRs with an increase in missed doses; 33/61 (54%) studies documenting the reasons for missed doses gave ADRs as a primary reason. No studies examined patterns of missed doses due to ADRs; 41/108 (38%) studies examined associations between 68 types of ADR (across 15 organ systems) and missed doses. Nuance around ADR‐missed doses relations regarding drug susceptibility testing profile and whether the missed doses originated from the patient, healthcare professionals, or both were found. Conclusion: There is extensive evidence that ADRs are a key driver for missed doses of anti‐TB treatment. Some papers examined specific ADRs and none evaluated the patterns of missed doses due to ADRs, demonstrating a knowledge deficit. Knowing why doses both are and are not missed is essential in providing targeted interventions to improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Camera‐based Driver Monitoring Systems (DMS) have the potential to exploit eye tracking correlates of alcohol intoxication to detect drunk driving. This study investigates how glance, blink, saccade, and fixation metrics are affected by alcohol, and whether possible effects remain stable across three different camera setups, as well as when the driver is out‐of‐the‐loop during level 4 automated driving (Wizard‐of‐Oz setup). Thirty‐five participants drove on a test track first sober and then with increasing intoxication levels reaching a breath alcohol concentration (BrAC) of 1‰. Linear Mixed‐Effects Regression analyses showed that with increasing intoxication levels, eye blinks became longer and slower, glances and fixations became fewer and longer, and more attention was directed to the road area, at the expense of more peripheral areas. Fixation and blink metrics were more robust to changes in automation mode, whereas glance‐based metrics were highly context dependent. Not all effects of alcohol intoxication could be measured with all eye tracking setups, where one‐camera systems showed lower data availability and higher noise levels compared to a five‐camera system. This means that lab findings based on higher quality eye tracking data might not be directly applied to production settings because of hardware limitations. [ABSTRACT FROM AUTHOR]

Nowadays, the focus of diabetes treatment has switched from lowering the glucose level to preserving glycemic homeostasis and slowing the disease progression. The main pathophysiology of both type 1 diabetes and long‐standing type 2 diabetes is pancreatic β‐cell mass loss and dysfunction. According to recent research, human pancreatic β‐cells possess the ability to proliferate in response to elevated insulin demands. It has been demonstrated that in insulin‐resistant conditions in humans, such as obesity or pregnancy, the β‐cell mass increases. This ability could be helpful in developing novel treatment approaches to restore a functional β‐cell mass. Treatment strategies aimed at boosting β‐cell function and mass may be a useful tool for managing diabetes mellitus and stopping its progression. This review outlines the processes of β‐cell failure and detail the many β‐cell abnormalities that manifest in people with diabetes mellitus. We also go over standard techniques for determining the mass and function of β‐cells. Lastly, we provide the therapeutic implications of utilizing antidiabetic drugs in controlling the mass and function of pancreatic β‐cells. [ABSTRACT FROM AUTHOR]

Aim: To investigate changes in the clinical characteristics of patients who abused benzodiazepine receptor agonists (BZRA) or over‐the‐counter (OTC) drugs before and after COVID‐19 based on the 2018 and 2022 data of the "Nationwide Psychiatric Hospital (NPH) Survey on Drug‐related Psychiatric Disorders." Method: A total of 446 and 155 cases, and 435 and 273 cases, who mainly abused BZRAs or OTC drugs, respectively, were extracted from the database of the two NPH Surveys. Demographic variables, education, employment, criminal record, drug use during the previous year, psychiatric diagnosis, and types of abused drugs were compared between 2018 and 2022. Result: A comparison of BZRA abusers revealed a decreased number of users during the previous year and an increase in the comorbidity rate of other disorders (F3 and F4 in ICD‐10) in 2022. Etizolam, flunitrazepam, triazolam, and zolpidem were used most in both years, with an increase in zolpidem and a decrease in triazolam in 2022. A comparison of OTC drug abusers revealed a higher proportion of women and young patients in 2022. An increase in the comorbidity rate of F3 and F9 and a significant increase in the use of dextromethorphan products were observed in 2022, although codeine products were in the majority in both years. Conclusion: By comparing NPH Surveys before and after the COVID‐19 pandemic, both BZRA abusers and OTC drug abusers present complex pathologies, requiring tailor‐made treatment. The younger OTC drug abusers were particularly evident among women, and the abuse of dextromethorphan‐containing OTC drugs has increased alarmingly. [ABSTRACT FROM AUTHOR]

New advancements in nanocarrier technologies are revolutionizing the delivery of drugs through the skin, allowing for precise treatment with better absorption, stability, and bioavailability. This review investigates lipid and inorganic nanocarriers like liposomes, ethosomes, and inorganic nanoparticles and assesses their potential for delivering drugs through the skin. It emphasizes the mechanisms that enable controlled release and deeper skin penetration, which are crucial for ensuring effectiveness in clinical applications. The review synthesizes existing research, acknowledging that only few nanocarriers are successfully deployed in clinical settings. By offering a comprehensive overview, it sheds light on the progress and future obstacles to using nanocarriers for drug delivery through the skin. [ABSTRACT FROM AUTHOR]

The article titled "Correction to 'Estimating the effects of prescription drug coverage for Medicare beneficiaries'" acknowledges errors in the original paper and provides corrected results. The errors were related to the coding of the generalized residual in the second stage of the two-stage residual inclusion estimator and the formulation for the standard error of the estimated moral hazard effect. The corrected results and additional details can be found in the appendices provided as online supporting information. The authors apologize for the errors. [Extracted from the article]

Pulmonary fibrosis represents the final alteration seen in a wide variety of lung disorders characterized by increased fibroblast activity and the accumulation of substantial amounts of extracellular matrix, along with inflammatory damage and the breakdown of tissue architecture. This condition is marked by a significant mortality rate and a lack of effective treatments. The depositing of an excessive quantity of extracellular matrix protein follows the damage to lung capillaries and alveolar epithelial cells, leading to pulmonary fibrosis and irreversible damage to lung function. It has been proposed that the connective tissue growth factor (CTGF) plays a critical role in the advancement of pulmonary fibrosis by enhancing the accumulation of the extracellular matrix and exacerbating fibrosis. In this context, the significance of CTGF in pulmonary fibrosis is examined, and a summary of the development of drugs targeting CTGF for the treatment of pulmonary fibrosis is provided. [ABSTRACT FROM AUTHOR]

Background: Orforglipron is a novel once‐daily oral non‐peptide glucagon‐like peptide‐1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta‐analysis has analyzed the efficacy and safety of orforglipron; this meta‐analysis aimed to address this knowledge gap. Methods: A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight. Results: From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow‐up duration of up to 36 weeks. Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD −5.48%, 95% CI [−7.64, −3.33], p < 0.01), 24 mg/day (MD −8.51%, 95% confidence interval (CI) [−9.88, −7.14], p < 0.01), 36 mg/day (MD −8.84%, 95% CI [−11.68, −6.00], p < 0.01) and 45 mg/day (MD −8.24%, 95% CI [−12.84, −3.63], p < 0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve >15% weight loss from baseline was significantly higher with orforglipron 24 mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], p = 0.0003), 36 mg/day (OR 17.43, 95% CI [3.18, 95.66], p = 0.001) and 45 mg/day (OR 23.17, 95% CI [4.37, 123.03], p = 0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side‐effects were predominant side effects, being dose‐dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones. Conclusion: Orforglipron at 24–45 mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24–36 mg/day is the most optimal dose for orforglipron as an anti‐obesity medicine. [ABSTRACT FROM AUTHOR]

Multiple treatment options exist for children with epilepsy, including surgery, dietary therapies, neurostimulation, and antiseizure medications (ASMs). ASMs are the first line of therapy, and more than 30 ASMs have U.S. Food and Drug Administration (FDA) approval for the treatment of various epilepsy and seizure types in children. Given the extensive FDA approval of ASMs in children, it is crucial to consider how the physiological and developmental changes throughout childhood may impact drug disposition. Various sources of pharmacokinetic (PK) variability from different extrinsic and intrinsic factors such as patients' size, age, drug–drug interactions, and drug formulation could result in suboptimal dosing of ASMs. Barriers exist to conducting clinical pharmacological studies in neonates, infants, and children due to ethical and practical reasons, limiting available data to fully characterize these drugs' disposition and better elucidate sources of PK variability. Modeling and simulation offer ways to circumvent traditional and intensive clinical pharmacology methods to address gaps in epilepsy and seizure management in children. This review discusses various physiological and developmental changes that influence the PK and pharmacodynamic (PD) variability of ASMs in children, and several key ASMs will be discussed in detail. We will also review novel trial designs in younger pediatric populations, highlight the role of extrapolation of efficacy in epilepsy, and the use of physiologically based PK modeling as a tool to investigate sources of PK/PD variability in children. Finally, we will conclude with current challenges and future directions for optimizing the efficacy and safety of these drugs across the pediatric age spectrum. [ABSTRACT FROM AUTHOR]

Aims: In Japan, the daily dosage of hypnotic drugs for insomnia treatment is increasing year by year, and over‐dependence on treatment with hypnotic drugs is a major problem. This study aimed to examine the factors related to the elimination of prescriptions of three or more hypnotic drugs within 1 year in our clinic. Methods: We conducted two surveys. Survey ① assessed the frequency of prescriptions of three or more hypnotic drugs by retrospectively reviewing the medical records of all patients who visited general and psychiatric outpatient clinics from January 2013 to March 2019. Survey ② assessed changes in prescriptions of hypnotic and psychotropic drugs within the subsequent year by retrospectively reviewing the medical records of all patients prescribed three or more hypnotic drugs who visited neuropsychiatric outpatient clinics multiple times between April 2013 and March 2019. Results: The frequency of prescribing three or more hypnotic drugs was six to nine times higher in psychiatry than in other departments. Flunitrazepam and brotizolam were the most common drugs prescribed and had the second lowest discontinuation rate after zolpidem. Conversely, eszopiclone, zopiclone, and suvorexant had the highest discontinuation rates. The success factors for drug reduction were age (odds ratio [OR]: 0.97, p < 0.0037), trazodone addition (OR: 12.86, p < 0.0194) and number of years of psychiatric experience. Conclusions: The characteristics and success factors in relation to drug reduction in patients with multiple prescriptions of hypnotic drugs identified in this study may contribute to solving the problem of multiple prescriptions of hypnotic drugs. [ABSTRACT FROM AUTHOR]

Objective: Most people with epilepsy (PWE) could live seizure‐free if treated with one or more antiseizure medications (ASMs). The World Health Organization (WHO) estimates that 75% of PWE in low‐resource settings lack adequate antiseizure treatment. Limited education surrounding epilepsy and the out‐of‐pocket costs of ASMs in particular pose barriers to managing epilepsy in resource‐poor, low‐income settings. The aim of this study is to implement and test a novel strategy to improve outcomes across the epilepsy care cascade marked by (1) retention in epilepsy care, (2) adherence to ASMs, and (3) seizure reduction, with the measured goal of seizure freedom. Methods: A randomized, double‐blinded clinical trial will be performed, centered at the Ignace Deen Hospital in Conakry, Republic of Guinea, in Western Sub‐Saharan Africa. Two hundred people with clinically diagnosed epilepsy, ages 18 years and above, will receive education on epilepsy and then be randomized to (i) free ASMs versus (ii) conditional cash, conditioned upon return to the epilepsy clinic. Participants will be followed for 360 days with study visits every 90 days following enrollment. Significance: We design a randomized trial for PWE in Guinea, a low‐resource setting with a high proportion of untreated PWE and a nearly completely privatized healthcare system. The trial includes a conditional cash transfer intervention, which has yet to be tested as a targeted means to improve outcomes for people with a chronic neurological disorder. The trial aims to provide an evidence base for the treatment of epilepsy in such settings. Plain Language Summary: We present a clinical trial protocol for a randomized, blinded study of 200 people with epilepsy in the low‐resource African Republic of Guinea, providing an educational intervention (E), and then randomizing in a 1:1 allocation to either free antiseizure medication (m) or conditional cash (c2) for 360 days. Measured outcomes include (1) returning to outpatient epilepsy care, (2) adherence to antiseizure medications (ASMs), and (3) reducing the number of seizures. This study is an initial look at giving small amounts of cash for desired results (or "nudges") for improving epilepsy outcomes in the sub‐Saharan African and brain disorder contexts. [ABSTRACT FROM AUTHOR]

Background: Many individuals worldwide continue to take benzodiazepine receptor agonists (BZRAs) long term (≥3 months). The aim of this study was to conduct a content analysis of the views and experiences of discontinuing long‐term BZRA use as documented in the free‐text responses of respondents to an online questionnaire examining mediators of behaviour change relating to the discontinuation of long‐term BZRA use. Design: The questionnaire was disseminated via online BZRA support groups to community‐based adults with either current or previous experience of long‐term BZRA use. The four free‐text questions focused on (1) barriers and (2) facilitators to discontinuing BZRA use; (3) additional supports required to discontinue BZRA use; and (4) additional comments regarding BZRA use. Response data were analysed using summative content analysis. Results: The most commonly reported barrier to BZRA discontinuation related to the consequences of stopping the medication, including withdrawal symptoms and the possibility of return of the original symptoms. The most common facilitator that respondents reported would help them in discontinuing BZRA use was support, primarily from medical professionals. Many respondents reported having been harmed or negatively affected in some way because of BZRA use. Several respondents expressed regret over ever taking BZRAs and/or reported that, with the benefit of hindsight, they should never have taken BZRAs in the first instance. Conclusion: The findings highlight the range of barriers faced by those attempting BZRA discontinuation and the importance of additional supports. Holistic and person‐centred approaches are needed to support discontinuation of long‐term BZRA use that considers an individual's personal circumstances and wider social context. Patient or Public Contribution: 'Experts by experience' with previous experience of long‐term BZRA use were involved in developing the questionnaire and writing the manuscript as collaborators. Individuals with lived experience of taking BZRAs completed the questionnaire. [ABSTRACT FROM AUTHOR]

Hepatic impairment (HI) moderately (<5‐fold) affects the systemic exposure (i.e., area under the plasma concentration–time curve [AUC]) of drugs that are substrates of the hepatic sinusoidal organic anion transporting polypeptide (OATP) transporters and are excreted unchanged in the bile and/or urine. However, the effect of HI on their AUC is much greater (>10‐fold) for drugs that are also substrates of cytochrome P450 (CYP) 3A enzymes. Using the extended clearance model, through simulations, we identified the ratio of sinusoidal efflux clearance (CL) over the sum of metabolic and biliary CLs as important in predicting the impact of HI on the AUC of dual OATP/CYP3A substrates. Because HI may reduce hepatic CYP3A‐mediated CL to a greater extent than biliary efflux CL, the greater the contribution of the former versus the latter, the greater the impact of HI on drug AUC ratio (AUCRHI). Using physiologically‐based pharmacokinetic modeling and simulation, we predicted relatively well the AUCRHI of OATP substrates that are not significantly metabolized (pitavastatin, rosuvastatin, valsartan, and gadoxetic acid). However, there was a trend toward underprediction of the AUCRHI of the dual OATP/CYP3A4 substrates fimasartan and atorvastatin. These predictions improved when the sinusoidal efflux CL of these two drugs was increased in healthy volunteers (i.e., before incorporating the effect of HI), and by modifying the directionality of its modulation by HI (i.e., increase or decrease). To accurately predict the effect of HI on AUC of hepatobiliary cleared drugs it is important to accurately predict all hepatobiliary pathways, including sinusoidal efflux CL. [ABSTRACT FROM AUTHOR]