Clinical Pharmacokinetics最新文献

{"title":"Plasma Concentrations of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Different Degrees of Obesity.","authors":"Danilo Menichelli, Arianna Pannunzio, Erminia Baldacci, Vittoria Cammisotto, Valentina Castellani, Rosaria Mormile, Ilaria Maria Palumbo, Antonio Chistolini, Francesco Violi, Job Harenberg, Daniele Pastori, Pasquale Pignatelli","doi":"10.1007/s40262-025-01474-8","DOIUrl":"10.1007/s40262-025-01474-8","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) has multiple cardio-metabolic comorbidities, including obesity. The use of direct oral anticoagulants (DOACs) in patients with AF and obesity is still uncertain owing to the concern of possible ineffective DOAC plasma concentration. We evaluated the peak and trough plasma concentrations of DOACs in AF patients with different degrees of obesity.</p><p><strong>Methods: </strong>Observational single-center study including patients with obesity and AF, between April 2022 and April 2024. Obesity was defined as body mass index (BMI) ≥ 30.0 kg/m². The 2-hour peak and trough DOAC plasma concentrations were assessed. Intake of DOAC was verified on site. Multivariable logistic regression analysis was used to assess the odds ratio (OR) and 95% confidence interval (95% CI) of factors associated with below-range trough concentration (BRTC) and below-range peak concentration (BRPC).</p><p><strong>Results: </strong>In total, 160 patients (33.8% women) with a mean age of 73.2 ± 9.1 years were included. The median BMI was 32.3 kg/m². DOACs prescribed were apixaban (46.8%), rivaroxaban (21.8%), dabigatran (16.4%), and edoxaban (15.0%); 18.1% and 14.4% had BRTC and BRPC concentrations, respectively. Patients with BRTC were more frequently treated with edoxaban and dabigatran and had a higher BMI. On multivariable logistic regression analysis, dabigatran [hazard ratio (HR) 3.039, 95% CI 1.155-7.999, p = 0.024) and BMI ≥ II class (OR 2.625, 95% CI 1.087-6.335, p = 0.032] were associated with BRTC. Dabigatran (OR 4.296, 95% CI 1.523-12.120, p = 0.006) and apixaban (OR 0.277, 95% CI 0.096-0.802, p = 0.018) were directly and inversely associated with BRPC, respectively.</p><p><strong>Conclusions: </strong>A nonnegligible proportion of patients with obesity and AF have below-range plasma concentrations of DOACs. Assessment of DOAC plasma concentration in obesity class ≥ II may be useful in these patients.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"453-462"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics of Cobicistat and its Effect on the Pharmacokinetics of the Anticancer Drug Olaparib.","authors":"Joanneke K Overbeek, Nielka P van Erp, David M Burger, Alfons A den Broeder, Stijn L W Koolen, Alwin D R Huitema, Rob Ter Heine","doi":"10.1007/s40262-025-01480-w","DOIUrl":"10.1007/s40262-025-01480-w","url":null,"abstract":"<p><strong>Objectives: </strong>Pharmacokinetic (PK) boosting is the intentional use of strong inhibitors of metabolic enzymes or transporters to boost the systemic exposure of a therapeutic drug. PK boosting is expanding to therapeutic areas outside human immunodeficiency virus (HIV) therapy. Data on the PK of the booster cobicistat and its effect on CYP3A-substrates outside of HIV therapy are lacking. This study aimed to describe the PK of once- and twice-daily cobicistat regimens in healthy volunteers and patients with rheumatoid arthritis, cancer, or HIV infection and to investigate the interplay between cobicistat and the anticancer drug olaparib.</p><p><strong>Methods: </strong>Cobicistat levels from 683 samples from 66 subjects in four clinical trials were included in the analysis. For olaparib, 261 samples from 12 subjects from one trial were included. Population PK analysis was performed by nonlinear mixed-effects modelling.</p><p><strong>Results: </strong>Both cobicistat and olaparib PK were adequately described by a well-stirred liver model with one central compartment and Erlang type absorption. Cobicistat PK was similar across patient populations and dosing regimens. Cobicistat increased olaparib prehepatic bioavailability 1.65-fold (RSE 6%) and decreased intrinsic clearance 0.34-fold (RSE 6.5%). A correlation between olaparib PK and cobicistat exposure could not be identified. The interindividual variability in olaparib clearance was lower with cobicistat than without cobicistat.</p><p><strong>Conclusions: </strong>The developed pharmacokinetic models adequately described cobicistat and olaparib plasma concentrations. PK boosting with cobicistat at 150 mg twice daily led to an increase in olaparib bioavailability and decrease in clearance. This effect was not correlated with cobicistat exposure, which may reflect saturation of the boosting effect of cobicistat at this dose.</p><p><strong>Trial registration numbers (date of registration): </strong>NCT02565888 (30-09-2015), NCT00825929 (19-01-2009), Netherlands Trial Register NL7766 (18-12-2018), NCT05078671 (22-09-2021).</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"425-435"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Solubility-Limited Absorption as a Surrogate to Predicting Positive Food Effect of BCS II/IV Drugs.","authors":"Karine Rodriguez-Fernandez, José David Gómez-Mantilla, Suneet Shukla, Peter Stopfer, Peter Sieger, Victor Mangas-Sanjuán, Sheila Annie Peters","doi":"10.1007/s40262-025-01473-9","DOIUrl":"10.1007/s40262-025-01473-9","url":null,"abstract":"<p><strong>Introduction and objective: </strong>Physiologically based pharmacokinetic (PBPK) models are increasingly used to predict food effect (FE) but model parameterization is challenged by in vitro-in vivo (IVIV) disconnect and/or parameter nonidentifiability. To overcome these issues, we propose a simplified PBPK model, in which all solubility-driven processes are lumped into a single parameter, solubility, which is optimized against observed concentration-time data.</p><p><strong>Methods: </strong>A set of commercially available biopharmaceutical classification system (BCS) II/IV compounds was selected to measure the solubility in a fasted state simulated intestinal fluid (FaSSIF) medium. The compounds were ranked from the lowest to the highest dose-adjusted FaSSIF solubility (FaSSIF/D) value and subdivided into three areas based on an upper and a lower limit: drugs with FaSSIF/D > upper limit having no FE, drugs with FaSSIF/D < lower limit having FE, and drugs between the limits said to be in the sensitivity range (SR), for which we tested the hypothesis that solubility-limited absorption (SLA) identified by simplified PBPK model can reliably predict positive FE if their exposures are not impacted by gut efflux or gut metabolism.</p><p><strong>Results: </strong>We demonstrate, using a subset of drugs within SR for which PBPK models were available, that drugs with SLA exhibited a positive FE, while those with no SLA did not show FE.</p><p><strong>Conclusions: </strong>This proposal allows for a reliable binary prediction of FE to enable timely decisions on the need for pilot FE studies as well as the timing of pivotal FE studies.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"373-385"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Influence of Ageing on the Pharmacodynamics and Pharmacokinetics of Chronically Administered Medicines in Geriatric Patients: A Review.","authors":"Nokwanda N Ngcobo","doi":"10.1007/s40262-025-01494-4","DOIUrl":"10.1007/s40262-025-01494-4","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"463"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to Rifampicin and its Metabolite 25-Deacetylrifampicin Rapidly Decreases During Tuberculosis Therapy.","authors":"Sylvain Goutelle, Olivier Bahuaud, Charlotte Genestet, Aurélien Millet, François Parant, Oana Dumitrescu, Florence Ader","doi":"10.1007/s40262-025-01479-3","DOIUrl":"10.1007/s40262-025-01479-3","url":null,"abstract":"<p><strong>Background and objective: </strong>Limited information is available on the pharmacokinetics of rifampicin (RIF) along with that of its active metabolite, 25-deacetylrifampicin (25-dRIF). This study aimed to analyse the pharmacokinetic data of RIF and 25-dRIF collected in adult patients treated for tuberculosis.</p><p><strong>Methods: </strong>In adult patients receiving 10 mg/kg of RIF as part of a standard regimen for drug-susceptible pulmonary tuberculosis enrolled in the Opti-4TB study, plasma RIF and 25-dRIF concentrations were measured at various occasions. The RIF and 25-dRIF concentrations were modelled simultaneously by using a population approach. The area under the concentration-time curves of RIF and 25-dRIF were estimated on each occasion of therapeutic drug monitoring. Optimal RIF exposure, defined as an area under the concentration-time curve over 24 hours/minimum inhibitory concentration > 435, was assessed.</p><p><strong>Results: </strong>Concentration data (247 and 243 concentrations of RIF and 25-dRIF, respectively) were obtained in 35 patients with tuberculosis (10 women, 25 men). Mycobacterium tuberculosis minimum inhibitory concentration ranged from 0.06 to 0.5 mg/L (median = 0.25 mg/L). The final model was a two-compartment model including RIF metabolism into 25-dRIF and auto-induction. Exposure to 25-dRIF was low, with a mean area under the concentration-time curve over 24 h ratio of 25-dRIF/RIF of 14 ± 6%. The area under the concentration-time curve over 24 h of RIF and 25-dRIF rapidly decreased during therapy, with an auto-induction half-life of 1.6 days. Optimal RIF exposure was achieved in only six (19.3%) out of 31 patients upon first therapeutic drug monitoring.</p><p><strong>Conclusions: </strong>Exposure to both RIF and 25-dRIF rapidly decreased during tuberculosis therapy. The contribution of 25-dRIF to overall drug exposure was low. Attainment of the target area under the concentration-time curve over 24 hours/minimum inhibitory concentration for RIF was poor, supporting an increased RIF dosage as an option to compensate for auto-induction.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"387-396"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Ageing on the Pharmacodynamics and Pharmacokinetics of Chronically Administered Medicines in Geriatric Patients: A Review.","authors":"Nokwanda N Ngcobo","doi":"10.1007/s40262-024-01466-0","DOIUrl":"10.1007/s40262-024-01466-0","url":null,"abstract":"<p><p>As people age, the efficiency of various regulatory processes that ensure proper communication between cells and organs tends to decline. This deterioration can lead to difficulties in maintaining homeostasis during physiological stress. This includes but is not limited to cognitive impairments, functional difficulties, and issues related to caregivers which contribute significantly to medication errors and non-adherence. These factors can lead to higher morbidity, extended hospital stays, reduced quality of life, and even mortality. The decrease in homeostatic capacity varies among individuals, contributing to the greater variability observed in geriatric populations. Significant pharmacokinetic and pharmacodynamic alterations accompany ageing. Pharmacokinetic changes include decreased renal and hepatic clearance and an increased volume of distribution for lipid-soluble drugs, which prolong their elimination half-life. Pharmacodynamic changes typically involve increased sensitivity to various drug classes, such as anticoagulants, antidiabetic and psychotropic medications. This review examines the primary age-related physiological changes in geriatrics and their impact on the pharmacokinetics and pharmacodynamics of medications.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"335-367"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Clinical Pharmacokinetics of Psilocin After Psilocybin Administration: A Systematic Review and Post‑Hoc Analysis.","authors":"Marije E Otto, Katelijne V van der Heijden, Jan W Schoones, Michiel J van Esdonk, Laura G J M Borghans, Gabriel E Jacobs, J G Coen van Hasselt","doi":"10.1007/s40262-025-01487-3","DOIUrl":"10.1007/s40262-025-01487-3","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"465"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Pharmacokinetics of Oral ALZ-801/Valiltramiprosate in a 2-Year Phase 2 Trial of APOE4 Carriers with Early Alzheimer's Disease.","authors":"John A Hey, Jeremy Y Yu, Susan Abushakra, Jean F Schaefer, Aidan Power, Pat Kesslak, Jijo Paul, Martin Tolar","doi":"10.1007/s40262-025-01482-8","DOIUrl":"10.1007/s40262-025-01482-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;ALZ-801/valiltramiprosate is an oral, small-molecule inhibitor of β-amyloid (Aβ) oligomer formation in late-stage development as a potential disease-modifying therapy for Alzheimer's disease (AD). ALZ-801, a valine-conjugated prodrug, is rapidly converted to tramiprosate after oral dosing. Upon conversion to tramiprosate, it generates a single metabolite, 3-sulfopropanoic acid (3-SPA). Both tramiprosate and 3-SPA are active anti-Aβ oligomer agents that mediate ALZ-801's central mechanism of action (MOA). We summarize herein the pharmacokinetics (PK) of ALZ-801 in apolipoprotein ε4 (APOE4) carrier subjects with early AD from a phase 2 trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The ALZ-801 phase 2 study was designed to evaluate longitudinal effects of ALZ-801 (265 mg BID) on plasma, cerebrospinal fluid (CSF) and volumetric magnetic resonance imaging (MRI) AD biomarkers, and clinical outcomes over 104 weeks in APOE4 carriers with early AD. Eighty-four subjects (31 APOE4/4 homozygotes and 53 APOE3/4 heterozygotes) with positive CSF biomarkers of amyloid and tau pathology were enrolled. The phase 2 study included a substudy of 24 subjects to provide 8-h steady-state PK at 65 weeks. Sparse PK samples were also analyzed. The relationships between plasma PK exposure and clinical characteristics [i.e., sex, APOE genotype, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), concomitant acetylcholinesterase inhibitor (AChEI) use, and tablet lot] were evaluated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The steady-state plasma PK results were closely aligned with the previous 2-week PK in the ALZ-801 phase 1b study in APOE4 carrier subjects with AD, as well as a phase 1 7-day PK study in heathy elderly volunteers. Following oral dosing, ALZ-801 was rapidly converted to the active moieties, tramiprosate and 3-SPA. The intersubject variability in plasma drug levels was low, confirming the superior performance of ALZ-801 versus oral tramiprosate tablet (150 mg BID) from the earlier tramiprosate phase 3 trials. Correlation analysis versus clinical characteristics showed that plasma exposures (Cmax and AUC8h) for ALZ-801, tramiprosate, and 3-SPA were not affected by sex, APOE genotype, age, BMI, concomitant AChEI use, or tablet lot. Plasma exposures of both tramiprosate and 3-SPA, but not ALZ-801, were inversely correlated with eGFR, in line with renal excretion as the primary route of elimination. ALZ-801 was well tolerated without new safety signals or events of amyloid-related imaging abnormalities (ARIA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The steady-state PK profile of oral ALZ-801 in subjects with early AD was not affected by sex, APOE genotype, age, BMI, concomitant use of AChEI, or tablet lot. The inverse relationship of plasma exposures of tramiprosate and 3-SPA, but not ALZ-801, versus eGFR is consistent with renal clearance as the primary route of elimination for tramiprosate and 3-SPA (active moieties), and wi","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"407-424"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Exploration and Physiologically Based Modelling of the Impact of Hepatic Impairment on Entrectinib Pharmacokinetics.","authors":"Agustos C Ozbey, Georgina Meneses-Lorente, Brian Simmons, Sam McCallum, Pieter Annaert, Neil Parrott, Kenichi Umehara","doi":"10.1007/s40262-024-01468-y","DOIUrl":"10.1007/s40262-024-01468-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>This study investigates the pharmacokinetics (PK) of entrectinib and its metabolite M5 (CYP3A4 substrates) in patients with hepatic impairment (HI) and applies physiologically based pharmacokinetic (PBPK) modelling to understand the observed changes mechanistically.</p><p><strong>Method: </strong>After a single oral administration of entrectinib at 100 mg, measured plasma concentrations for entrectinib and M5 in control subjects and HI patients were compared to predictions made with Simcyp^®. Model sensitivity analyses explored the possible reasons for mismatches to observed data. Reduced oral absorption due to lower bile salt (BS) levels in the intestinal lumen in hepatic impairment was examined.</p><p><strong>Results: </strong>Physiologically based pharmacokinetic model simulations overestimated the 80% increase in entrectinib area under the plasma concentration curve between 0h to infinity (AUC_inf) observed in patients with severe HI, predicting a > 2-fold rise. Observed maximal plasma concentration (C_max) increased by 25% from controls to mild HI but decreased by 61% from mild to severe HI. Although the model predicted C_max within a 2-fold range, there was a trend to greater over-prediction with increasing HI severity. For M5, PBPK modelling did not capture the observed trends well. The C_max and AUC_inf were overestimated in HI patients and the trend to reduction of C_max with minimal change in AUC_inf with increasing severity of HI was not well captured. Decreasing Simcyp^® default luminal BS concentrations by 2-, 6-, and 8.7-fold for mild, moderate, and severe HI improved the predictions for both entrectinib and M5.</p><p><strong>Conclusion: </strong>Physiologically based pharmacokinetic model simulations tended to overestimate the observed moderate changes in entrectinib exposures due to HI. For improved prediction of poorly soluble lipophilic drugs like entrectinib there is a need for PBPK models of HI to account for additional pathophysiological changes such as reduced intestinal BS levels.</p><p><strong>Trial registration: </strong>NCT number: NCT04226833.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"437-451"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Opioid Infusions in the Adult Intensive Care Unit Setting-A Systematic Review.","authors":"Johannie Beaucage-Charron, Justine Rinfret, Guillaume Trottier, Marie-Maxim Sévigny, Lisa Burry, Amélie Marsot, David Williamson","doi":"10.1007/s40262-025-01490-8","DOIUrl":"10.1007/s40262-025-01490-8","url":null,"abstract":"<p><strong>Introduction: </strong>Pharmacokinetics (PKs) of drugs are often altered in the intensive care unit (ICU). Opioids are often used in the ICU, particularly as continuous infusions, and their characteristics lead them to undergo PK alterations. We conducted a systematic review to assess the PK of opioid infusions in the ICU.</p><p><strong>Methods: </strong>Embase, MEDLINE, PubMed, CINAHL, and Evidence-Based Medicine Reviews (EBMR) were searched from inception to March 2024. Studies were included if they evaluated PKs of opioid infusions in adult patients in the ICU. Two reviewers independently selected and extracted data.</p><p><strong>Results: </strong>Out of the 1040 records screened, 17 studies were included. Five studies were conducted on fentanyl, seven on morphine, one on hydromorphone, two on remifentanil, two on alfentanil, and one on sufentanil. Most studies where observational studies or case series. The mean age was 56 years old. Duration of the infusion varied between 3 h and 20 days. PKs of fentanyl, sufentanil, and hydromorphone were significantly impaired, whereas the PKs of morphine, alfentanil, and remifentanil were impaired to a lesser degree. The PK parameter that was most affected by critical illness was the half-life (T½).</p><p><strong>Conclusions: </strong>To counter these PK alterations, new therapeutic avenues must be further explored in the ICU to individualize opioid infusions.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"323-334"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}