Clinical Pharmacokinetics最新文献

{"title":"Clinical Pharmacokinetics of Antitubercular Drugs in the Overweight and Obese Population: Implications for Dosage Adjustments.","authors":"Marlene Prager, Valentin Al Jalali, Markus Zeitlinger","doi":"10.1007/s40262-024-01442-8","DOIUrl":"10.1007/s40262-024-01442-8","url":null,"abstract":"<p><p>The rise in global obesity prevalence has increased the need to understand the pharmacokinetics of drugs in overweight and obese individuals. Tuberculosis remains a significant health challenge, and its treatment outcomes can be influenced by the pharmacokinetic profiles of antitubercular agents. This literature review aims to point out the clinical pharmacokinetics of antitubercular drugs in the overweight and obese patient population, highlighting considerations for potential dosage adjustments. We conducted a comprehensive search of the PubMed US National Library of Medicine from inception to January 2024. Articles focusing on the pharmacokinetics of antitubercular agents used for both drug-susceptible and multidrug-resistant tuberculosis in overweight and obese adults were included. In total, 349 scientific articles were identified and examined for human pharmacokinetic parameters. Of these, 19 were included in this article. To highlight potential differences, pharmacokinetic data for normal-weight tuberculosis patients are also presented, albeit selectively. In general, pharmacokinetic studies of antitubercular agents in overweight and obese individuals are lacking. Fixed-dose combinations often used in the treatment of drug-susceptible tuberculosis are not recommended when treating these population groups. Rather, individual dosing based on therapeutic drug monitoring and the known solubility of the substance should be considered. To improve the management of tuberculosis in overweight and obese patients, there is an urgent need for pharmacokinetic studies and, ultimately, adequate dosing in this patient population, especially given the increasing prevalence of obesity.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"193-214"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945775","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 Telmisartan in Healthy Subjects and Hypertensive Patients.","authors":"In Hwan Jeong, Sooyoon Ryu, Nayoung Han, Christine E Staatz, In-Hwan Baek","doi":"10.1007/s40262-024-01471-3","DOIUrl":"10.1007/s40262-024-01471-3","url":null,"abstract":"<p><strong>Background and objective: </strong>Telmisartan exhibits significant pharmacokinetic (PK) variability, but it remains unclear whether its PK profile is altered in hypertensive patients. This study aimed to characterize telmisartan PKs by conducting a meta-analysis and developing a pooled population PK model based on data from healthy subjects and hypertensive patients.</p><p><strong>Methods: </strong>Relevant literature was identified by a systematic approach. Eighteen studies were selected for analysis, which included 394 healthy subjects receiving single doses of telmisartan, 190 healthy subjects receiving repeated doses, along with 295 hypertensive patients receiving repeated doses. Pooled population PK analysis incorporated 20 mean concentration-time profiles from 14 studies. Meta-analyses were performed using OpenMeta-Analyst, and population PK modeling was performed using NONMEM^®.</p><p><strong>Results: </strong>Repeated telmisartan doses increased peak plasma concentrations. However, other noncompartmental PK parameters remained consistent across healthy and hypertensive populations. Telmisartan PKs were best described using a two-compartment model with first-order absorption and elimination in pooled analysis. Typical PK parameter values for apparent clearance (CL/F), apparent central and peripheral volumes of distribution (V₁/F and V₂/F), absorption rate constant (k_a), and absorption lag time were 18.3 L/h, 20.7 L, 360 L, 0.183 h^-1 and 0.228 h, respectively. Interindividual variabilities in CL/F, V₁/F, and k_a were 84%, 122%, and 106%, respectively. Covariate analysis revealed significantly lower CL/F (63.7%) and V₁/F (90.3%) values in hypertensive patients than healthy subjects.</p><p><strong>Conclusion: </strong>These findings quantified the variability of telmisartan PK profile and highlighted the differences between healthy individuals and hypertensive patients, suggesting the need for optimized dosage strategies to improve therapeutic outcomes.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"285-295"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977809","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":"Physiologically Based Pharmacokinetic Model of Cefotaxime in Patients with Impaired Renal Function.","authors":"Fatima Zbib, Anthéa Deschamps, Lionel Velly, Olivier Blin, Romain Guilhaumou, Florence Gattacceca","doi":"10.1007/s40262-024-01469-x","DOIUrl":"https://doi.org/10.1007/s40262-024-01469-x","url":null,"abstract":"<p><strong>Background: </strong>Cefotaxime is a widely prescribed cephalosporin antibiotic used to treat various infections. It is mainly eliminated unchanged by the kidney through tubular secretion and glomerular filtration. Therefore, a reduction of kidney function may increase exposure to the drug and induce toxic side effects.</p><p><strong>Objectives: </strong>The objectives of this study were to develop a physiologically based pharmacokinetic (PBPK) model of cefotaxime in healthy European adults, to mechanistically describe the impact of chronic kidney disease (CKD) on cefotaxime pharmacokinetics, and to assess the applicability of the model to patients requiring intensive care.</p><p><strong>Methods: </strong>Using PK-Sim^® software, we developed a PBPK model for cefotaxime, including basolateral and apical renal transporters and renal esterases, in healthy subjects and then extrapolated to patients with CKD by incorporating pathophysiological changes and reductions in activity of drug-metabolizing enzymes and transporters into the model. We then evaluated the predictive performance of the model in patients requiring intensive care using clinical routine data.</p><p><strong>Results: </strong>Model predictions were considered adequate in healthy subjects and patients with CKD, with predicted-to-observed area under the curve ratios within the two-fold acceptance criterion. Mean prediction error and mean absolute prediction error did not exceed ± 30 and 30%, respectively, except in patients with stage 4 CKD, where they were 70.5 and 75.6%, respectively. The model showed good predictive performance when applied to patients requiring intensive care, but its clinical applicability in this population needs to be further evaluated.</p><p><strong>Conclusion: </strong>We successfully developed whole-body PBPK models to predict cefotaxime pharmacokinetics in different populations. These models represent an additional step toward improving personalized cefotaxime dosing regimens in vulnerable populations.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":"64 2","pages":"257-273"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064134","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":"Population Pharmacokinetics of Meropenem Across the Adult Lifespan.","authors":"Angelique E Boutzoukas, Stephen J Balevic, Marion Hemmersbach-Miller, Patricia L Winokur, Kenan Gu, Austin W Chan, Michael Cohen-Wolkowiez, Thomas Conrad, Guohua An, Carl M J Kirkpatrick, Geeta K Swamy, Emmanuel B Walter, Kenneth E Schmader, Cornelia B Landersdorfer","doi":"10.1007/s40262-024-01465-1","DOIUrl":"10.1007/s40262-024-01465-1","url":null,"abstract":"<p><strong>Background and objective: </strong>We conducted an opportunistic pharmacokinetic study to evaluate the population pharmacokinetics of meropenem, an antimicrobial commonly used to treat Gram-negative infections in adults of different ages, including older adults, and determined optimal dosing regimens.</p><p><strong>Methods: </strong>A total of 99 patients were included. The population pharmacokinetic models used had two compartments: zero-order input and linear elimination. Covariates evaluated included renal function, body size, age, sex, vasopressor use, and frailty, using the Canadian Study of Health and Aging Clinical Frailty score (in patients aged ≥ 65 years). We simulated optimal dosing regimens by renal function and by age group to achieve therapeutic target attainment.</p><p><strong>Results: </strong>Participants' ages ranged from 20 to 95 years, with an average age of 57.4 years, and 22% (23/103) were aged ≥ 75 years. Creatinine clearance had the greatest impact on the clearance of meropenem. After accounting for renal function and body size, no other covariates resulted in a significant impact on the pharmacokinetics of meropenem. Simulations indicated that patients with normal renal function achieved ≥ 90% target attainment only for organisms with minimum inhibitory concentrations (MICs) ≤ 4 mg/L using the least strict surrogate target of unbound concentration > MIC (fT_>MIC) for 40% of the dosing interval. For the conservative target fT_>4xMIC for 100% of the dosing interval, extended infusion may be required even for organisms with MICs up to 0.25 mg/L. Patients with renal impairment could achieve ≥ 90% target attainment for more resistant organisms, but extended infusion did not increase the MICs up to which target attainment could be achieved.</p><p><strong>Conclusions: </strong>Meropenem dosing should be based on renal function rather than age. For patients without renal impairment, extended infusion may increase the probability of target attainment.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"229-241"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834336","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":"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":"https://doi.org/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":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Pharmacokinetics and Safety of Remdesivir in Phase I Participants with Varying Degrees of Renal Impairment.","authors":"Haeyoung Zhang, Rita Humeniuk, Sean Regan, Yiannis Koullias, Santosh Davies, Amy John, Gong Shen, Deqing Xiao, Robert H Hyland, Helen Winter, Aryun Kim","doi":"10.1007/s40262-024-01453-5","DOIUrl":"10.1007/s40262-024-01453-5","url":null,"abstract":"<p><strong>Background and objective: </strong>Remdesivir is a nucleotide analog prodrug approved for the treatment of COVID-19. This study evaluated the pharmacokinetics and safety of remdesivir and its metabolites (GS-704277 and GS-441524) in participants with varying degrees of renal impairment. Results of this phase I study, along with those of a phase III study, contributed to an extension of indication for remdesivir in the USA and Europe for use in patients with COVID-19 with all stages of renal impairment, including those on dialysis, with no dose adjustment.</p><p><strong>Methods: </strong>This phase I, open-label, parallel-group study enrolled participants who had mild (n = 12), moderate (n = 11), or severe (n = 10) renal impairment or kidney failure (n = 6 with dialysis, n = 4 without dialysis). Healthy matched controls were enrolled as reference. Remdesivir was given as single intravenous doses of 100 mg (mild and moderate renal impairment), 40 mg (severe renal impairment, kidney failure predialysis), and 20 mg (kidney failure postdialysis and without dialysis).</p><p><strong>Results: </strong>Plasma pharmacokinetics of remdesivir were not affected by mild, moderate, or severe renal impairment or kidney failure. Geometric least squares mean ratios ranged from 0.8 to 1.2 for remdesivir area under the plasma concentration-time curve (AUC). GS-704277 AUC was up to 2.8-fold higher and GS-441524 AUC up to 7.9-fold higher in participants with renal impairment. Adverse events and laboratory abnormalities were consistent with the existing safety profile for remdesivir.</p><p><strong>Conclusions: </strong>Observed pharmacokinetics for remdesivir and its metabolites in participants with renal impairment aligned with expected changes based on known routes of elimination. Remdesivir was generally safe and well tolerated in participants with renal impairment, and no new safety concerns were identified. These results, along with those from the phase III study in patients with COVID-19 with severely reduced kidney function, support the use of remdesivir in patients with any degree of renal impairment with no dose adjustments.</p><p><strong>Trial registration: </strong>EudraCT no. 2020-003441-10; 9 July 2020.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"67-78"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674933","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":"Static Versus Dynamic Model Predictions of Competitive Inhibitory Metabolic Drug-Drug Interactions via Cytochromes P450: One Step Forward and Two Steps Backwards.","authors":"Ivan Tiryannik, Aki T Heikkinen, Iain Gardner, Anthonia Onasanwo, Masoud Jamei, Thomas M Polasek, Amin Rostami-Hodjegan","doi":"10.1007/s40262-024-01457-1","DOIUrl":"10.1007/s40262-024-01457-1","url":null,"abstract":"<p><strong>Background: </strong>Predicting metabolic drug-drug interactions (DDIs) via cytochrome P450 enzymes (CYP) is essential in drug development, but controversy has reemerged recently about whether in vitro-in vivo extrapolation (IVIVE) using static models can replace dynamic models for some regulatory filings and label recommendations.</p><p><strong>Objective: </strong>The aim of this study was to determine if static and dynamic models are equivalent for the quantitative prediction of metabolic DDIs arising from competitive CYP inhibition.</p><p><strong>Methods: </strong>Drug parameter spaces were varied to simulate 30,000 DDIs between hypothetical substrates and inhibitors of CYP3A4. Predicted area under the plasma concentration-time profile ratios for substrates (AUCr = AUC_{(presence of precipitant)}/AUC_{(absence of precipitant)}) were compared between dynamic simulations (Simcyp^® V21) and corresponding static calculations, giving an inter-model discrepancy ratio (IMDR = AUCr_dynamic/AUCr_static). Dynamic simulations were conducted using a 'population' representative and a 'vulnerable patient' representative with maximal concentration (C_max) or average steady-state concentration (C_avg,ss) as the inhibitor driver concentrations. IMDRs outside the interval 0.8-1.25 were defined as discrepancy between models.</p><p><strong>Results: </strong>The highest rate of IMDR <0.8 and IMDR >1.25 discrepancies in the 'population' representative was 85.9% and 3.1%, respectively, when using C_avg,ss as the inhibitor driver concentration. Using the 'vulnerable patient' representative showed the highest rate of IMDR >1.25 discrepancies at 37.8%.</p><p><strong>Conclusion: </strong>Static models are not equivalent to dynamic models for predicting metabolic DDIs via competitive CYP inhibition across diverse drug parameter spaces, particularly for vulnerable patients. Caution is warranted in drug development if static IVIVE approaches are used alone to evaluate metabolic DDI risks.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"155-170"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799569","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: Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer.","authors":"Daping Zhang, Adekemi Taylor, Jie Janet Zhao, Christopher J Endres, Ariel Topletz-Erickson","doi":"10.1007/s40262-024-01458-0","DOIUrl":"10.1007/s40262-024-01458-0","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"171-172"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806287","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":"Echinocandins Pharmacokinetics: A Comprehensive Review of Micafungin, Caspofungin, Anidulafungin, and Rezafungin Population Pharmacokinetic Models and Dose Optimization in Special Populations.","authors":"Marta Albanell-Fernández","doi":"10.1007/s40262-024-01461-5","DOIUrl":"10.1007/s40262-024-01461-5","url":null,"abstract":"<p><p>In recent years, many population pharmacokinetic (popPK) models have been developed for echinocandins to better understand the pharmacokinetics (PK) of these antifungals. This comprehensive review aimed to summarize popPK models of echinocandins (micafungin, caspofungin, anidulafungin, and rezafungin), by focusing on dosage optimization to maximize the probability of attaining the PK/PD target proposed in special populations. A search in PubMed, Embase, Web of Science, and Scopus, supplemented by the bibliography of relevant articles, was conducted from inception to March 2024, including both observational and prospective trials. A total of 1126 articles were identified, 47 of them were included in the review (22 for micafungin, 13 for caspofungin, 9 for anidulafungin, and 3 for rezafungin). A two-compartment model was more frequently used to describe the PK parameters of echinocandin (78.7% of developed models), although more complex structural models with three and four compartments have also been developed. The covariates to estimate the PK parameters such as clearance (CL) and volume of distribution (V_d) differed between models. Weight total (WT) was the most frequently reported to be a significant predictor for both parameters, especially for estimating the CL in pediatrics. The PD parameter most widely reported assessing the drug exposure-efficacy relationship was the area under the concentration-time curve to minimum inhibitory concentration (MIC) ratio (AUC_0-24/MIC) with different targets proposed for each echinocandin. In certain populations such as patients that are critically ill, obese, receiving extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), or pediatric patients and/or patients with cancer or that are immunocompromised, the fixed dosing strategies recommended in the drug prescribing information may not reach the PK/PD target. For these populations, different strategies have been proposed, such as a dosing regimen based on body weight or increasing the loading and/or maintenance dose. Despite echinocandins' favorable safety profile and predictable PK, certain groups at risk of suboptimal drug exposure can benefit from therapeutic drug monitoring (TDM) to prevent clinical failures. Numerous popPK models of echinocandins have been developed. However, an external validation of the suggested dosing regimens in conjunction with an analysis of population subgroups should be conducted before implementing a popPK model in clinical practice.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"27-52"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871597","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}