Clinical Pharmacokinetics最新文献

{"title":"Correction: Population Pharmacokinetic Analysis of Enalapril and Enalaprilat in Newly Treated Children with Heart Failure: Implications for Safe Dosing of Enalapril (LENA Studies).","authors":"Melina Steichert, Willi Cawello, Stephanie Laeer","doi":"10.1007/s40262-026-01677-7","DOIUrl":"10.1007/s40262-026-01677-7","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1275"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618071","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":"ALBI Grade is a Determinant of Lenvatinib Pharmacokinetics, Efficacy, and Toxicities in Japanese Patients with Hepatocellular Carcinoma.","authors":"Kosuke Suzuki, Yumi Otoyama, Natsumi Matsumoto, Yusuke Masuo, Yoko Nakajima, Ikuya Sugiura, Takahiro Fuji, Erika Nomura, Yuki Ichikawa, Yuu Shimozuma, Manabu Uchikoshi, Momoka Hayano, Mayuko Hanano, Remi Murase, Chika Mitomori, Kiyoshi Oka, Masashi Sakaki, Yukio Kato, Hitoshi Yoshida, Ken-Ichi Fujita","doi":"10.1007/s40262-026-01662-0","DOIUrl":"10.1007/s40262-026-01662-0","url":null,"abstract":"<p><strong>Background and objective: </strong>The doses of lenvatinib for patients with hepatocellular carcinoma (HCC) are determined using the Child-Pugh classification and body weight. Because lenvatinib is highly bound to plasma albumin (98.6%), patients with low plasma albumin levels and hepatic lenvatinib clearance may exhibit a high unbound fraction and/or concentration of lenvatinib in the plasma to alter efficacy and toxicity. This study exploratorily and prospectively examined the effects of baseline albumin-bilirubin (ALBI) on systemic exposure to unbound lenvatinib and lenvatinib clinical responses in patients with HCC.</p><p><strong>Patients and methods: </strong>Patients with HCC who received lenvatinib were enrolled. Total- and unbound-base dose-normalized area under the plasma concentration-time curve (AUCt/dose and AUCu/dose, respectively) were determined. Progression-free survival (PFS) and toxicities were evaluated.</p><p><strong>Results: </strong>Forty-one patients were enrolled between May 2020 and January 2024. AUCu/dose, but not AUCt/dose, was significantly negatively correlated with ALBI score (P = 0.00699). Patients with ALBI grade ≥ 2b had significantly higher AUCu/dose than those with < 2b (mean ± SD, 0.00602 ± 0.00268 vs. 0.00390 ± 0.00168 h/L, P = 0.0131). Child-Pugh class was associated with AUCu/dose (P = 0.0312); however, among Child-Pugh classification components, albumin only was associated with the AUCu/dose. Multivariate Cox proportional hazards analysis identified ALBI grade ≥ 2b as risk factor for shorter PFS (P = 0.0000521; hazard ratio 9.43; 95% confidence interval 3.18-28.0). ALBI grade ≥ 2b, but not Child-Pugh class, showed a significantly higher incidence of lenvatinib-induced toxicity grades ≥ 2 than ALBI grade < 2b (87.0 vs. 55.6%, P = 0.0357).</p><p><strong>Conclusion: </strong>The study exploratorily found that baseline ALBI grade was associated with lenvatinib AUCu/dose and clinical responses.</p><p><strong>Trial registration number: </strong>UMIN000057138 (registered on February 27, 2025).</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1229-1241"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307325","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":"Elranatamab Population Pharmacokinetics and Exposure-Response for Cytokine Release Syndrome in Patients with Relapsed or Refractory Multiple Myeloma.","authors":"Jennifer E Hibma, Donald Irby, Alan Liu, Mohamed Elmeliegy, Lindsay E King, David Gifondorwa, Sibo Jiang, Kamrine E Poels, Pooneh Soltantabar, Hoi-Kei Lon, Blerta Shtylla, Diane Wang, Jason H Williams, Timothy Nicholas","doi":"10.1007/s40262-026-01663-z","DOIUrl":"10.1007/s40262-026-01663-z","url":null,"abstract":"<p><strong>Background and objective: </strong>A population pharmacokinetics (PopPK) model was developed for elranatamab, a bispecific antibody targeting both B-cell maturation antigen (BCMA) and cluster of differentiation 3 (CD3), to characterize the PopPK of elranatamab and guide clinical development. Elranatamab is approved in several countries for the treatment of relapsed or refractory multiple myeloma.</p><p><strong>Methods: </strong>The PopPK model incorporated data from four clinical studies and described both free and total elranatamab as well as soluble BCMA (sBCMA) using a semi-mechanistic two-compartment target-binding model. In total there were 13,233 observations from 321 participants who received intravenous (IV) or subcutaneous (SC) elranatamab monotherapy with doses ranging from 0.1 to 1000 µg/kg.</p><p><strong>Results: </strong>Elranatamab exhibited approximately linear PK over the dose range evaluated (i.e., 6-76 mg SC), with limited cellular target-mediated drug disposition and generally proportional exposure, with modest deviations at very high baseline sBCMA. None of the potential covariates evaluated, including age, sex, body weight, baseline sBCMA, and immunogenicity, were found to be clinically significant predictors of elranatamab exposure. Exposure-response analyses identified early peak exposure and tumor burden as key predictors of cytokine release syndrome (CRS), primarily after the first step-up dose. Simulations supported restarting treatment without re-priming after dose interruptions of up to 12 weeks.</p><p><strong>Conclusion: </strong>These findings support the approved fixed-dose regimen and provide a framework for clinical management of elranatamab in relapsed or refractory multiple myeloma.</p><p><strong>Clinical trial registration: </strong>NCT03269136, NCT04798586, NCT04649359, NCT05014412.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1173-1192"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249550","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":"Informing Sampling Design for Lung Distribution Studies Using a Pulmonary Population Minimal PBPK Model.","authors":"Haini Wen, Muhammad Waqas Sadiq, Markus Fridén, Jens M Hohlfeld, Lena E Friberg, Elin M Svensson","doi":"10.1007/s40262-026-01664-y","DOIUrl":"10.1007/s40262-026-01664-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Understanding intrapulmonary pharmacokinetics (PK) following inhalation remains a significant challenge in drug development and repurposing. Current lung sampling methods include bronchoalveolar lavage (BAL), biopsies, and the more recent bronchosorption technique, which enhances regional specificity while reducing potential quantification errors. This study aimed to develop a pulmonary population physiologically based pharmacokinetic (PBPK) model for inhaled salbutamol by integrating data from all three sampling techniques to improve PK predictions and to compare different sampling strategies to optimize future study designs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A population-based minimal PBPK model was developed using data from a previously published study (NCT03524066) investigating salbutamol's pulmonary and plasma PK in 13 healthy volunteers after inhalation. Simulations assessed the impact of permeability on pulmonary PK profiles and BAL-derived epithelial lining fluid (ELF)-to-plasma ratios using salbutamol as a reference compound. Stochastic simulation-estimation (SSE) methods were employed to assess the feasibility of different sampling strategies for estimating key parameters of the PBPK model. First, we evaluated using one or two sampling techniques within a single bronchoscopy session. Second, we compared uniform and staggered bronchosorption-based sampling strategies for drugs from different permeability categories.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The minimal PBPK model described pulmonary PK of salbutamol across the lung and estimated the unbound tissue-plasma partition coefficient for the lung ( &lt;math&gt;&lt;msub&gt;&lt;mi&gt;K&lt;/mi&gt; &lt;mrow&gt;&lt;mtext&gt;p&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mtext&gt;u&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mtext&gt;lung&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; ) and the effective permeability ( &lt;math&gt;&lt;msub&gt;&lt;mi&gt;P&lt;/mi&gt; &lt;mtext&gt;eff&lt;/mtext&gt;&lt;/msub&gt; &lt;/math&gt; ) of salbutamol as 11.0 and 0.543 m/h, respectively. Inter-individual variabilities (IIV) were found on plasma clearance and lung deposition fraction. No significant IIV was detected on &lt;math&gt;&lt;msub&gt;&lt;mi&gt;K&lt;/mi&gt; &lt;mrow&gt;&lt;mtext&gt;p&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mtext&gt;u&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mtext&gt;lung&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; or &lt;math&gt;&lt;msub&gt;&lt;mi&gt;P&lt;/mi&gt; &lt;mtext&gt;eff&lt;/mtext&gt;&lt;/msub&gt; &lt;/math&gt; . Simulations indicated that low-permeability drugs exhibited higher concentrations in the ELF, while high-permeability drugs accumulated more in lung tissues, after inhalation. Results from SSE showed that bronchosorption plus biopsy were the most informative two-technique combination and bronchosorption alone was the best single-technique option. Additionally, the optimal sampling strategy for both uniform and staggered sampling depended on drug permeability, with early time points favoured for high-permeability drugs and later or broader windows needed for low-permeability drugs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;A pulmonary population PBPK model for inhaled salbutamol was developed by integrating detailed intrapulmonary data f","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1257-1272"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344141","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":"Quantitative Pharmacology Justifying Ribociclib Dose in Early Breast Cancer.","authors":"Yan Ji, Craig Wang, Francois Pierre Combes, Yu-Yun Ho, Peter A Fasching, Michael Untch, Juan Pablo Zarate, John Crown","doi":"10.1007/s40262-026-01643-3","DOIUrl":"10.1007/s40262-026-01643-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Ribociclib was recently approved for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer (EBC) at the starting dose of 400 mg orally once daily (3 weeks on/1 week off), following previous approval in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer at the starting dose of 600 mg orally once daily (3 weeks on/1 week off). This study aims to characterize ribociclib pharmacokinetics and its relationship with QT interval corrected according to Fridericia's formula (QTcF) in patients with EBC and justify the dose in EBC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data from several studies, including the pivotal phase III trial in patients with EBC and phase I-III trials in patients with advanced breast cancer and advanced cancer were analyzed. Ribociclib pharmacokinetics was characterized by non-compartmental or population pharmacokinetic analyses. The exposure-QTcF relationship was assessed by linear mixed-effects modeling. Neutropenia and QTcF data were compared by dose and population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At the 400-mg dose, ribociclib steady-state clearance was ~ 20% higher in patients with EBC than patients with advanced cancer, suggesting differences in pharmacokinetics between populations. Steady-state mean area under the plasma concentration-time curve and maximum (peak) plasma drug concentration were ~ 50% lower and steady-state clearance was ~ 50% higher in patients with EBC receiving 400 mg compared with patients with advanced cancer and advanced breast cancer receiving 600 mg, attributed to differences in both dose and population. The pharmacokinetic-QTcF analysis showed that the patient population was a significant covariate in QTcF response. The model-estimated mean change from baseline in QTcF at steady-state maximum (peak) plasma drug concentration was substantially lower in patients with EBC receiving 400 mg (10.0 ms) versus in patients with advanced breast cancer receiving 600 mg (20.7-23.7 ms), likely due to the dose and pharmacokinetic exposure effect and the population effect. Patients with EBC receiving 400 mg experienced lower rates and severity of both neutropenia and QTcF prolongation than patients with advanced breast cancer receiving 600 mg.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This integrative analysis characterized the ribociclib pharmacokinetic and exposure-QTcF relationship, revealed the population effect on both pharmacokinetic and QTcF response, and justified the 400-mg dose in EBC. This work illustrates the utility and impact of quantitative pharmacology in justifying different doses across different patient populations for oncology therapies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical trial registration: &lt;/strong&gt;NATALEE (NCT03701334, 2018-09-21); AMALEE (NCT03822468, 2019-01-28); MONALEESA-2 (NCT01958021, 2013-10-04); MONALEESA-3 (NCT02422615, 2015-04-01); MONALEESA-7 (NCT02278120, ","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1217-1228"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301228","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":"Revisited Pharmacokinetic Profiles of Methylprednisolone in Plasma and Urine After Single and Multiple Oral Administrations: Relevance in Sports Drug Testing.","authors":"Sergi Coll, Claudia Bressan, Núria Monfort, Ana Aldea-Perona, Marcel Lí Carbó, Rosa Ventura","doi":"10.1007/s40262-026-01665-x","DOIUrl":"10.1007/s40262-026-01665-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The pharmacokinetic profiles of methylprednisolone (MP) in plasma and urine were evaluated after single and multiple oral doses. MP is prohibited in sports competitions when administered systemically (oral, injectable, or rectal administrations) whereas other routes remain permitted for therapeutic purposes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of this study was to characterize the urinary MP excretion after oral administration to assess whether the current World Anti-Doping Agency minimum reporting level of 30 ng/mL in urine is appropriate for distinguishing permitted from prohibited administrations, as well as whether the recommended washout period is adequate. Another aim was to better define MP elimination kinetics and evaluate its systemic effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Sixteen healthy male participants were enrolled and divided into two groups. One group received a single oral dose of 12 mg of MP, while the other received 12 mg daily for 3 consecutive days. Urine and blood samples were collected before, during, and after administration. Urine samples were analyzed for MP and 15 metabolites using a sensitive and selective liquid chromatography-tandem mass spectrometry method. Plasma samples were analyzed for unchanged MP and cortisol using liquid chromatography-tandem mass spectrometry. A pharmacokinetic analysis was performed using a one-compartment model with first-order absorption, combining plasma concentrations and urinary excretion data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;MP represented only a small proportion of the administered dose, confirming that metabolism is the main elimination pathway. After a single oral dose, urinary MP concentrations above 30 ng/mL were observed up to 12 h, while all samples collected later were below this concentration. After multiple dosing, most samples above 30 ng/mL were also found within 12 h, although a few participants still showed concentrations above the minimum reporting level in the 12 to 24 h period. All samples collected more than 24 h after the last dose were below 30 ng/mL. In plasma, MP reached peak concentrations around 1.6-2.3 h after administration and was not detectable 24 h after the last dose. Cortisol concentrations were markedly suppressed after dosing, with recovery to baseline within 24-48 h depending on the regimen.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study confirms that the current urinary minimum reporting level of 30 ng/mL is appropriate for detecting oral MP use while minimizing the risk of false adverse analytical findings. The results also support the adequacy of the current 3-day washout period. Modern liquid chromatography-tandem mass spectrometry analysis and combined plasma-urine pharmacokinetic modeling provided robust evidence that MP is rapidly eliminated, extensively metabolized, and associated with transient cortisol suppression after oral administration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical trial registration: &lt;/strong&gt;EudraCT nu","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1243-1256"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315616","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":"Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide.","authors":"Mette J F Nielsen, Niels-Peter Becker, Helene H Hansen Duus, Katrine Kirkeby, Viera Kupčová, Britt W Lauenborg, Benjamin Low, Olivia Svolgaard, Louise Witten","doi":"10.1007/s40262-026-01654-0","DOIUrl":"10.1007/s40262-026-01654-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Cagrilintide is a long-acting amylin agonist under development as monotherapy for weight management and as a fixed-dose combination with the glucagon-like peptide-1 receptor agonist semaglutide (CagriSema) for weight management and treatment of type 2 diabetes. Two studies were conducted to assess the effects of renal or hepatic impairment on pharmacokinetics, safety and tolerability following single doses of cagrilintide.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In both studies, adult participants were categorised into four groups on the basis of renal or hepatic function (normal function and mild, moderate or severe impairment) and received a single dose of cagrilintide 0.6 or 0.9 mg, respectively. The primary endpoint was area under the cagrilintide plasma concentration curve from time zero extrapolated to infinity (AUC&lt;sub&gt;0-∞&lt;/sub&gt;) from baseline (day 1) to day 36 (renal impairment study) or day 39 (hepatic impairment study). Other pharmacokinetic parameters included maximum observed cagrilintide plasma concentration (C&lt;sub&gt;max&lt;/sub&gt;), time to C&lt;sub&gt;max&lt;/sub&gt; (t&lt;sub&gt;max&lt;/sub&gt;) and safety.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The renal impairment study included 33 participants (normal function, n = 14; mild impairment, n = 7; moderate impairment, n = 7; severe impairment, n = 5) and the hepatic impairment study included 32 participants (normal function, n = 14; mild impairment, n = 7; moderate impairment, n = 7; severe impairment, n = 4). In both studies, total cagrilintide exposure (AUC&lt;sub&gt;0-∞&lt;/sub&gt;), C&lt;sub&gt;max&lt;/sub&gt; and other pharmacokinetic parameters were similar across groups with no consistent patterns observed with renal or hepatic impairment. Compared with normal renal function, the estimated ratio of the mean AUC&lt;sub&gt;0-∞&lt;/sub&gt; was 1.23 (90% confidence interval [CI], 0.91-1.66) in mild impairment, 1.18 (0.87-1.59) in moderate impairment and 1.21 (0.87-1.68) in severe impairment. Compared with normal hepatic function, the estimated ratio of the mean AUC&lt;sub&gt;0-∞&lt;/sub&gt; was 0.99 (0.89-1.11) in mild impairment, 1.01 (0.91-1.12) in moderate impairment and 1.11 (0.96-1.30) in severe impairment. Overall, 21 and 16 treatment-emergent adverse events (TEAEs) were reported in 11 and 9 participants in the renal and hepatic studies, respectively. In both studies, no serious TEAEs, TEAEs leading to study withdrawal or deaths were reported. No increase in number of adverse events with increasing renal or hepatic impairment was observed, and no new safety or tolerability findings with cagrilintide were identified with renal or hepatic impairment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In these studies, within the limitations of small sample sizes, no clinically relevant differences in cagrilintide pharmacokinetics were observed in participants with renal or hepatic impairment compared with those with normal function, suggesting that dose adjustment is not warranted for these populations. Cagrilintide was well-tolerated a","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1087-1099"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142928","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 Pharmacokinetic Analysis of Glecaprevir and Pibrentasvir in Pediatric Patients ≥ 3 to < 18 Years of Age with Genotypes 1-6 Chronic Hepatitis C Virus (HCV) Infection.","authors":"Neha Thakre, Denise Beck, Ahmed M Saeed, Doerthe Eckert, Mong-Jen Chen, Wei Liu, Hoi Kei Lon, Nael M Mostafa, Sven Mensing","doi":"10.1007/s40262-026-01637-1","DOIUrl":"10.1007/s40262-026-01637-1","url":null,"abstract":"<p><strong>Background: </strong>Mavyret, a combination medication of glecaprevir (GLE) and pibrentasvir (PIB), is approved to treat chronic and acute hepatitis C virus (HCV) (genotypes 1-6) infection in adults and pediatric patients ≥ 3 years old. To support approval, a two-part clinical trial was conducted in adolescents (≥ 12 to < 18 years) and children (≥ 3 to < 12 years) to identify the appropriate dosage and determine the efficacy and safety in pediatric patients.</p><p><strong>Objectives: </strong>Population pharmacokinetic (popPK) analyses reported herein aimed to (1) characterize the pharmacokinetic (PK) parameters of orally administered GLE and PIB and the sources of PK variability in pediatric patients and (2) support the use of a body weight-based pediatric GLE/PIB dose ratio of 50/20 mg in HCV-infected children.</p><p><strong>Methods: </strong>PopPK models were built for GLE and PIB independently using nonlinear mixed-effects modeling and utilized data collected from 126 pediatric patients. Demographic, pathophysiological, and treatment factors were investigated for their impact on GLE and PIB PK.</p><p><strong>Results: </strong>PopPK analyses of pediatric exposures confirmed comparable exposures to those of adults who achieved over 95% sustained virologic response (SVR12). The pediatric popPK model incorporated allometric body weight-based scaling and subsequently identified no covariate that significantly impacted GLE exposures. Similarly, no covariate beyond the specified allometric body weight scaling was identified to impact PIB exposures. The developed pediatric popPK models were able to describe the central tendency and variability of the data.</p><p><strong>Conclusion: </strong>These results supported the approval of body weight-based dosing regimens of GLE and PIB in children (< 45 kg) infected with any HCV genotype.</p><p><strong>Clinical trials: </strong>NCT03067129.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1061-1072"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027541","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 Pharmacokinetic Modelling of Dolutegravir: A Narrative Review.","authors":"Émilie Pilote, Nancy L Sheehan, Amélie Marsot","doi":"10.1007/s40262-026-01653-1","DOIUrl":"10.1007/s40262-026-01653-1","url":null,"abstract":"<p><p>Dolutegravir-based regimens are part of the preferred regimens in all populations living with HIV, but dolutegravir's pharmacokinetics can vary greatly with factors such as drug-drug interactions (DDIs) and age. For example, DDIs between dolutegravir and rifamycins in countries with a high burden of HIV/tuberculosis co-infection present a major challenge. Attaining therapeutic concentrations is crucial for virologic success and to prevent resistance. Understanding dolutegravir pharmacokinetics and its sources of variability is essential to ensure adequate exposure in all individuals. Population pharmacokinetic (PopPK) modeling is a powerful tool for characterizing medication disposition. In this review, we aim to synthesize existing dolutegravir PopPK models, highlighting key pharmacokinetic parameters and covariate effects. A literature search was done on Medline and Embase databases from inception to November 18th, 2025. This review included 23 studies: 15 in adults, 4 in pediatrics, 2 in pregnancy (mothers and their newborn), and 2 in term neonates. Almost all models included allometric scaling, with body weight especially, on apparent clearance (CL/F) and/or apparent volume of distribution (Vd/F) parameters. When considering differences in body size, CL/F and Vd/F were similar across populations. The absorption rate constant (k_a) was higher in adults and presented high variability across populations. Other common covariates in adults and pediatrics were co-medications and background antiretrovirals. Data and tested covariates were limited in pregnant women and neonates. Study simulations and predefined target values indicated adequate recommended dolutegravir doses. Further characterization of dolutegravir PopPK in populations at risk of altered concentrations (e.g., preterm neonates, pediatrics, pregnancy, obesity, and older adults) is crucial to better understand dolutegravir pharmacokinetics in these populations as data are still limited.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"953-993"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351174","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":"Correction: Model‑Based Alternative Dosing Strategies for Subcutaneous Nivolumab to Improve Cost Effectiveness.","authors":"Yan Wang, Laura H Bukkems, Rob Ter Heine, J G C van Hasselt, S L W Koolen, J J M A Hendrikx, Tom Van der Hulle, Ellen Kapiteijn, Juliette Zwaveling, Annemarie Becker, Michel M van den Heuvel, Willemijn S M E Theelen, Thijs H Oude Munnink, Egbert F Smit, Henk-Jan Guchelaar, Dirk Jan A R Moes","doi":"10.1007/s40262-026-01649-x","DOIUrl":"10.1007/s40262-026-01649-x","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1113-1114"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971166","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}