Clinical Pharmacology in Drug Development最新文献

{"title":"Comparative Analysis of Therapeutic Methods for Sudden Sensorineural Hearing Loss.","authors":"Lingling Di, Hui Yong, Zhikai Wang, Yu Zhou, Huaitao Liu, Shijie Wei","doi":"10.1002/cpdd.1576","DOIUrl":"https://doi.org/10.1002/cpdd.1576","url":null,"abstract":"<p><p>This prospective study compared the therapeutic efficacy of Ginaton alone, Ginaton combined with glucocorticoids, or Ginaton with mouse nerve growth factor (mNGF) in patients with sudden sensorineural hearing loss (SSNHL). Between January 2014 and June 2015, 101 SSNHL patients, with treatment initiated 3-10 days post onset, were randomly assigned to receive 1 of 3 2-week regimens: Ginaton alone (n = 33), Ginaton + glucocorticoid (n = 34), or Ginaton + mNGF (n = 34). Primary outcome was overall hearing improvement. Effectiveness rates were 78.79% (95% confidence interval [CI] 61.8%-89.9%) for Ginaton, 79.41% (95% CI 62.9%-90.1%) for Ginaton + glucocorticoid, and 88.24% (95% CI 72.5%-95.8%) for Ginaton + mNGF; these differences were not statistically significant (P > .05). All 3 groups showed significant post-treatment reductions in whole blood viscosity (high, medium, low shear rates; all P < .01), low-density lipoprotein cholesterol (all P < .01), and triglycerides (all P < .01). The neutrophil-to-lymphocyte ratio, an inflammatory marker, significantly decreased in the Ginaton + glucocorticoid (P < .05) and Ginaton + mNGF groups (P < .01). While all regimens demonstrated positive effects on hearing and surrogate markers, and Ginaton + mNGF showed a numerically higher hearing improvement rate, no statistically superior regimen for overall hearing was identified. This study suggests these approaches improve inner ear blood rheology and inflammation. However, larger, placebo-controlled trials are crucial to confirm efficacy and elucidate the distinct pharmacological contributions of each component, considering the study's sample size and open-label design.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Bioequivalence, and Safety of Levothyroxine Sodium Tablets in Healthy Chinese Subjects.","authors":"Juan Jin, Chunrong Huang, Fangliang Gan, Tuo Li, Lina Wang, Xiaolu Wang, Xiali Rao, Jufang Liu","doi":"10.1002/cpdd.1564","DOIUrl":"https://doi.org/10.1002/cpdd.1564","url":null,"abstract":"<p><p>Recently, a local pharmaceutical company produced levothyroxine sodium tablets, an endogenous drug that helps improve water-salt metabolism and reduce myxedema. However, the bioequivalence of these tablets is not well known. The present study aimed to investigate the bioequivalence, pharmacokinetics, and safety of a single oral dose of 2 levothyroxine sodium tablets in healthy adult Chinese subjects under fasting conditions. The study used a single-center randomized, single-dose, 2-sequence, 4-period replicate crossover design. Forty-eight subjects fasted for at least 10 hours before taking the medication. According to the literature, levothyroxine sodium is an endogenous narrow therapeutic index drug; therefore, baseline samples were collected before administration in healthy adult subjects. Blood specimens from all subjects were collected against the light within 48 hours to detect levothyroxine concentration in serum. A noncompartmental model was used for the analysis of pre- and post-baseline correction pharmacokinetic parameters. The geometric mean ratio of the post-baseline correction maximum plasma concentration and area under the concentration-time curve from time 0 to 48 hours with a 90% confidence interval was calculated. The final data met the bioequivalence criteria. No serious adverse reactions were found, suggesting that the test and reference preparations of levothyroxine sodium tablets have a similar safety profile.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Early Phase Innovation—Adapting to the New Age of Accelerated Drug Approvals","authors":"Amalia M. Issa","doi":"10.1002/cpdd.1578","DOIUrl":"10.1002/cpdd.1578","url":null,"abstract":"<p>The landscape of early-phase drug development is evolving rapidly, driven by both scientific innovation and the increasing adoption of accelerated approval pathways worldwide. The US Food and Drug Administration's (FDA) newly announced Commissioner's National Priority Voucher (CNPV) program marks a potentially transformative moment for drug development in the United States.<span>¹</span> By offering a radically shortened review timeline—compressing the traditional 10-12 months to just 1-2 months for qualifying applications—the FDA signals both a commitment to innovation and a willingness to rethink its regulatory paradigms to meet urgent national health needs.</p><p>As the FDA unveils its new CNPV program, it is worth considering how the traditional playbook for early-phase drug development might be rewritten. For clinical pharmacologists and drug developers, the CNPV program could fundamentally alter the early-phase landscape in several ways.</p><p>Although the potential benefits are substantial, several questions remain. The program's initial rollout is limited —a 1-year pilot with a small number of vouchers—so its broader impact will depend on future expansion and the resolution of implementation uncertainties, such as selection criteria and transparency. There is also the perennial concern of ensuring that speed does not come at the expense of scientific rigor or patient safety, a balance the FDA insists will be maintained through multidisciplinary review and ongoing sponsor communication.<span>^{3, 4}</span></p><p>The CNPV program represents a bold step toward modernizing regulatory science and aligning drug development incentives with national health priorities. For early-phase developers, it offers both an opportunity and a challenge: to be ready, nimble, and aligned with the evolving priorities of public health. If successful, the program may serve as a blueprint for future regulatory innovation, catalyzing faster access to transformative therapies while upholding the highest standards of safety and efficacy.</p><p>As the pilot unfolds, the clinical pharmacology community will watch closely, eager to see whether this “tumor board” model can deliver on its promise and perhaps redefine what is possible in early-phase drug development.</p><p>The author declares no conflicts of interest.</p><p>No funding was obtained for this work.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 8","pages":"570-571"},"PeriodicalIF":1.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1578","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Honoring the Extensive and Impactful Contributions of Prof David J Greenblatt, MD: Founding Editor of Clinical Pharmacology in Drug Development","authors":"Vikram Arya,&nbsp;Michael Fossler,&nbsp;Oliver Grundmann","doi":"10.1002/cpdd.1575","DOIUrl":"10.1002/cpdd.1575","url":null,"abstract":"&lt;p&gt;Clinical pharmacology is an interdisciplinary field that encompasses laboratory research, drug development, therapeutic optimization, and patient care. Among the giants in the field of clinical pharmacology stands Prof David Greenblatt, a visionary, pioneer, and highly influential scientist and mentor. Fueled by passion, dedication, and a tireless resolve to venture into uncharted territories, Dr Greenblatt's unparalleled contributions have significantly advanced the discipline of clinical pharmacology.&lt;/p&gt;&lt;p&gt;A native of Newton, Massachusetts, Dr Greenblatt is a magna cum laude graduate of Amherst College (1966). He graduated from Harvard Medical School in 1970, then trained in internal medicine at the Montefiore Hospital, New York City (1970-1971), and on the Harvard Medical Service at Boston City Hospital (1971-1972). Following a fellowship in Clinical Pharmacology at Massachusetts General Hospital under the mentorship of Dr Jan Koch-Weser (1972-1974), he stayed on to head their Clinical Pharmacology Unit (1975-1979). Dr Greenblatt has been on the faculty of the Tufts University School of Medicine (TUSM) and the staff of Tufts Medical Center since 1979. He is a senior faculty member in the Graduate Program in Pharmacology and Drug Development and has previously served as chair of the Department of Pharmacology and Experimental Therapeutics at TUSM, program director and associate program director of the institution's Clinical/Translational Research Center, and chair of the Institutional Review Board. He has served as a postdoctoral training supervisor or dissertation supervisor for more than 60 trainees, most of whom have gone on to positions as university-based investigators or scientists in industry.&lt;/p&gt;&lt;p&gt;In his inspiring, tireless, and accomplished career journey spanning more than 5 decades, Dr Greenblatt has significantly contributed essential knowledge to expand our understanding of drug interactions and pharmacokinetic principles, especially in the field of psychopharmacology and psychiatry. Dr Greenblatt has been recognized for his exemplary contributions to clinical pharmacology by major national and international scientific organizations. He received the McKeen Cattell Award from the American College of Clinical Pharmacology (ACCP) in 1985, the Distinguished Service Award in 2001, the Distinguished Investigator Award in 2002, and the Hartmut Derendorf Mentorship in Clinical Pharmacology Award in 2024.&lt;/p&gt;&lt;p&gt;Dr Greenblatt joined ACCP in 1974 and is one of the longest-serving fellows in ACCP history. After joining the Board of Regents in 1981, he was elected as president-elect in 1994-1996 and served as president from 1996 to 1998. Having completed his terms on the Board and Executive Committee, he became an honorary regent and has actively engaged with ACCP in numerous ways. He has served on the Nominations and Publications Committees, on the Working Groups for Online Communities, Pearls for Practice, and Revenue Sources. Having aut","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 8","pages":"568-569"},"PeriodicalIF":1.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 and Exposure-Response Analysis of the Cognitive Effects of TAK-071 in Participants With Parkinson Disease and Cognitive Impairment.","authors":"Hongxia Jia, Axel Facius, Rachel Jennings, Yaming Hang, Jaya Padmanabhan, Niraj M Shanbhag, Brian T Harel, Arthur Simen, Wei Yin","doi":"10.1002/cpdd.1579","DOIUrl":"https://doi.org/10.1002/cpdd.1579","url":null,"abstract":"<p><p>TAK-071 is a novel muscarinic M₁ positive allosteric modulator under investigation for the treatment of cognitive impairment and falls associated with Parkinson disease (PD). This study evaluated population pharmacokinetics of TAK-071 following single (1-160 mg) and multiple (3-15 mg once daily) oral-dose TAK-071 in 112 healthy participants and 53 participants with PD from Phase 1 and Phase 2 studies. A 1-compartment model with a delayed absorption phase adequately described TAK-071 pharmacokinetics. Age, body weight, dose, and formulation were significant covariates. Model simulations indicated that age-adjusted dosing is unnecessary. An exposure-response relationship on cognitive function (attention, executive function, memory, global) was evaluated. Benefits were observed on attention, executive function, and global cognition, and these plateaued between 5 and 7.5 mg once daily, supporting a dose of 7.5 mg for future clinical studies, as 7.5 mg was well tolerated. As patients with PD can have an increased risk of falls, the relationship between cognitive function and risk of falls, as assessed by stride time variability, was explored. Cognition response for the attention domain score showed consistent and sustained improvement in stride time variability compared with when no response was observed, supporting further investigation of TAK-071 in PD for the risk of falls.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Pharmacodynamic Bioequivalence Study of Enoxaparin Sodium 100 mg/1 mL Solution for Injection in Prefilled Syringe in Healthy Volunteers Under Fasting Conditions.","authors":"Naba Kumar Talukdar, Shailesh Sonar, Nisha Pal, Uilberson Silva","doi":"10.1002/cpdd.1565","DOIUrl":"https://doi.org/10.1002/cpdd.1565","url":null,"abstract":"<p><p>This study evaluated the bioequivalence of enoxaparin sodium 100 mg/1 mL solution for injection in a prefilled syringe manufactured by a generic company was compared with the reference product of the same dosage form, in healthy adult volunteers under fasting conditions. The comparison focused on pharmacodynamic (PD) parameters. This open-label, randomized, balanced, 2-treatment, 2-period, single-dose, crossover study involved 60 healthy volunteers. No serious adverse events were reported. Chromogenic assay techniques were used for sample analysis. The linearity range for PD parameters was from 0.100 to 0.800 IU/mL for anti-factor IIa activity, from 0.100 to 0.800 IU/mL for anti-factor Xa activity, and from 750.000 to 10,000.000 pg/mL for tissue factor pathway inhibitor quantification. Statistical analysis was conducted using SAS software Version 9.4. The PD parameters evaluated included maximum observed activity concentration, area under the effect curve from time 0 to time t, median time to maximum concentration, and terminal elimination half-life for anti-factor Xa and anti-factor IIa activity. The 95% confidence intervals for the geometric mean ratio of log-transformed PD parameters between the test and reference products for anti-factor Xa and anti-factor IIa activities were within the range of 80%-125%. It was concluded that the test formulation is bioequivalent to the reference formulation of 100 mg/1 mL solution for injection in a prefilled syringe, under fasting conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Safety, and Tolerability of Different Maintenance Dose Regimens of Mosnodenvir (JNJ-1802) in Healthy Adult Participants.","authors":"Thomas N Kakuda, Nicole Harasym, Annemie Buelens, Ariane Kahnt, Caroline Feys, Ami Nilsson, Nele Goeyvaerts, Tristan Baguet, Tine De Marez, Guillermo Herrera-Taracena, Freya Rasschaert","doi":"10.1002/cpdd.1574","DOIUrl":"https://doi.org/10.1002/cpdd.1574","url":null,"abstract":"<p><p>Dengue virus infection has become a global health concern, and no dengue-specific treatment is available. Mosnodenvir is a pan-serotypic dengue antiviral in clinical development. In this Phase 1, open-label study (NCT05201937), high- and low-dose weekly, and twice weekly maintenance doses (MDs) of mosnodenvir were evaluated following a twice daily loading dose (LD) over 2 days. The utility of a convenient capillary blood sampling device (TASSO-M20) was also explored. Healthy adults were sequentially assigned to receive: 450 mg twice daily LD, 900 mg once weekly MD; 450 mg twice daily LD, 450 mg twice weekly MD; 150 mg twice daily LD, 300 mg once weekly MD; or 150 mg twice daily LD, 150 mg twice weekly MD. Mosnodenvir exposure rapidly increased with LD and was maintained during the MD phase. In general, mosnodenvir increased in a dose-proportional manner with similar areas under the concentration-time curve between once weekly and twice weekly MD. The mean terminal elimination half-life across treatments was 6.7-8.7 days, supporting less frequent dosing. Safety and tolerability were similar across all treatment regimens. TASSO-M20 was preferred over venipuncture by participants. In summary, mosnodenvir administered weekly or biweekly achieved pharmacokinetic exposures that were found to be safe and well tolerated.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and Bioequivalence Evaluation of Two Sitagliptin Tablets With Different Salts in Healthy Subjects","authors":"Usok Hyun,&nbsp;Seongnam Chu,&nbsp;Sungyun Kim,&nbsp;Jung-Ki Hong,&nbsp;Taeyoung Kim,&nbsp;In-Soo Yoon,&nbsp;Jung-Jin Kim,&nbsp;Hyun-Jong Cho","doi":"10.1002/cpdd.1573","DOIUrl":"10.1002/cpdd.1573","url":null,"abstract":"<p>The objective of the current study was to evaluate the rate and extent of absorption of a test formulation (sitagliptin hydrochloride) and a reference formulation (sitagliptin phosphate). An open-label, randomized, single-dose, single-center, 2-sequence, 2-period, and cross-over phase 1 study was implemented to assess the pharmacokinetic bioequivalence of the test and reference formulations containing a single dose of sitagliptin 100 mg in 32 healthy volunteers under fasting conditions. The differences between the test and reference formulations in terms of the area under the curve from dosing to the time of the last measured concentration (AUC_last) and the maximum concentration (C_max) were found to be not significant. The 90% confidence intervals of sitagliptin Ln-transformed AUC_last and C_max were within the pharmacokinetic bioequivalence acceptance range of 80%-125%. The test formulation with sitagliptin hydrochloride was bioequivalent to the reference formulation with sitagliptin phosphate in healthy male volunteers under fasting conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 10","pages":"781-786"},"PeriodicalIF":1.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies to Manage Dosing Deviations and Interruptions of Cabotegravir Long-Acting Intramuscular Injections.","authors":"Kelong Han, Ronald D D'Amico, William R Spreen, Susan L Ford","doi":"10.1002/cpdd.1568","DOIUrl":"https://doi.org/10.1002/cpdd.1568","url":null,"abstract":"<p><p>Long-acting cabotegravir is approved for HIV treatment and prevention. To guide management of dosing deviations and interruptions, concentration-time profiles for monthly and every 2 months regimens were simulated using a population pharmacokinetic (PPK) model. Adequate exposure was defined as trough concentration (C_tau) >0.45 µg/mL (observed 5th percentile of first C_tau in pivotal studies) in >95% of subjects and maximum concentration (C_max) <13.1 µg/mL (highest observed median steady-state C_max in previous studies) in >50% of subjects. Simulations showed: (1) median C_max remained ≤6.35 µg/mL after doubled doses; (2) C_tau was suboptimal after half dose at first injection but recovered with a corrective dose; (3) injection delays ≤7 days maintained adequate C_tau, while longer delays caused extended low-exposure periods (≤23 days for 1-month delay, ≤83 days for 3-month delay); (4) reinitiating loading dose after delays >1 month led to higher exposure than continuing injections and may mitigate efficacy loss and resistance risks; and (5) oral bridging (30 mg daily) maintained adequate exposure during delays. Recommended strategies include no action for higher-than-planned doses, corrective dosing for lower-than-planned doses, strict adherence to schedule, reinitiating the loading dose after delays >1 month, and oral bridging. These findings were incorporated into product labeling and can inform next-generation cabotegravir and other long-acting agent development.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Modeling to Evaluate Drug-Drug Interactions of Tacrolimus With Ritonavir, a CYP3A Irreversible Inhibitor: Applications for Dosing Optimization in Transplant Patients","authors":"Yanjun Jiang,&nbsp;Lu Wang,&nbsp;Jia Liu,&nbsp;Lizhen Jiang,&nbsp;Kang Li,&nbsp;Zhanhui Lv,&nbsp;Sufeng Zhou,&nbsp;Feng Shao","doi":"10.1002/cpdd.1572","DOIUrl":"10.1002/cpdd.1572","url":null,"abstract":"<p>Immunosuppressant tacrolimus is frequently coadministered with other drugs in clinical practice. Ritonavir is a CYP3A irreversible inhibitor that is used in combination with nirmatrelvir for the treatment of COVID-19 in nirmatrelvir/ritonavir. We aimed to apply physiologically based pharmacokinetic (PBPK) modeling to investigate the dose adjustment strategy for tacrolimus during short-term coadministration with ritonavir. PBPK models for tacrolimus and ritonavir were successfully developed based on in vitro and clinical data, and were used to predict drug-drug interaction levels via metabolic enzyme inhibition mechanisms. The recommended dose strategy based on our model simulation is to hold tacrolimus during nirmatrelvir/ritonavir treatment and restart half of the initial dose on day 3 after the 5-day ritonavir course, followed by resuming the full dose on day 5. This administration strategy can maintain trough concentrations of tacrolimus within the therapeutic window during and after ritonavir treatment.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 10","pages":"797-808"},"PeriodicalIF":1.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}