Clinical Pharmacokinetics最新文献

{"title":"Comment on: Anti-Coagulant Treatment of Cancer-Associated Thrombosis in Frail Patients: Impact of Frailties on the Management of Drug-Drug Interactions.","authors":"Lorenz Van der Linden, Thomas Vanassche, Lucas Van Aelst, Peter Verhamme","doi":"10.1007/s40262-023-01344-1","DOIUrl":"10.1007/s40262-023-01344-1","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485265","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":"Maternal Ezetimibe Concentrations Measured in Breast Milk and Its Use in Breastfeeding Infant Exposure Predictions.","authors":"Cindy H T Yeung, Julie Autmizguine, Pooja Dalvi, Audrey Denoncourt, Shinya Ito, Pamela Katz, Mehzabin Rahman, Yves Theoret, Andrea N Edginton","doi":"10.1007/s40262-023-01345-0","DOIUrl":"10.1007/s40262-023-01345-0","url":null,"abstract":"<p><strong>Background: </strong>Lactating mothers taking ezetimibe, an antihyperlipidemic agent, may be hesitant to breastfeed despite the known benefit of breastfeeding to both mother and infant. Currently, no data exist on the presence or concentration of ezetimibe and its main active metabolite, ezetimibe-glucuronide (EZE-glucuronide), in human breast milk.</p><p><strong>Methods: </strong>Voluntary breast milk samples containing ezetimibe and EZE-glucuronide were attained from lactating mothers taking ezetimibe as part of their treatment. An assay was developed and validated to measure ezetimibe and EZE-glucuronide concentrations in breast milk. A workflow that utilized a developed and evaluated pediatric physiologically based pharmacokinetic (PBPK) model, the measured concentrations in milk, and weight-normalized breast milk intake volumes was applied to predict infant exposures and determine the upper area under the curve ratio (UAR).</p><p><strong>Results: </strong>Fifteen breast milk samples from two maternal-infant pairs were collected. The developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay showed an analytical range of 0.039-5.0 ng/mL and 0.39-50.0 ng/mL for ezetimibe and EZE-glucuronide, respectively. The measured concentrations in the breast milk samples were 0.17-1.02 ng/mL and 0.42-2.65 ng/mL of ezetimibe and EZE-glucuronide, respectively. The evaluated pediatric PBPK model demonstrated minimal exposure overlap in adult therapeutic dose and breastfed infant simulated area under the concentration-time curve from time zero to 24 h (AUC₂₄). Calculated UAR across infant age groups ranged from 0.0015 to 0.0026.</p><p><strong>Conclusions: </strong>PBPK model-predicted ezetimibe and EZE-glucuronide exposures and UAR suggest that breastfeeding infants would receive non-therapeutic exposures. Future work should involve a 'mother-infant pair study' to ascertain breastfed infant plasma ezetimibe and EZE-glucuronide concentrations to confirm the findings of this work.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566845","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":"Salivary Therapeutic Drug Monitoring of Antimicrobial Therapy: Feasible or Futile?","authors":"Lina Davies Forsman, Hannah Yejin Kim, Thi Anh Nguyen, Jan-Willem C Alffenaar","doi":"10.1007/s40262-024-01346-7","DOIUrl":"10.1007/s40262-024-01346-7","url":null,"abstract":"<p><p>Personalised drug dosing through therapeutic drug monitoring (TDM) is important to maximise efficacy and to minimise toxicity. Hurdles preventing broad implementation of TDM in routine care include the need of sophisticated equipment and highly trained staff, high costs and lack of timely results. Salivary TDM is a non-invasive, patient-friendly alternative to blood sampling, which has the potential to overcome barriers with traditional TDM. A mobile UV spectrophotometer may provide a simple solution for analysing drug concentrations in saliva samples. Salivary TDM utilising point-of-care tests can support personalised dosing in various settings including low-resource as well as remote settings. In this opinion paper, we describe how hurdles of implementing traditional TDM may be mitigated by salivary TDM with new strategies for patient-friendly point-of-care testing.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650379","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":"Pharmacokinetics, Disposition, and Biotransformation of [¹⁴C]Lenacapavir, a Novel, First-in-Class, Selective Inhibitor of HIV-1 Capsid Function, in Healthy Participants Following a Single Intravenous Infusion.","authors":"Elijah Weber, Raju Subramanian, William Rowe, Michael Graupe, John Ling, Gong Shen, Rebecca Begley, Jennifer Sager, Scott Wolckenhauer, Martin Rhee, Ramesh Palaparthy, Renu Singh","doi":"10.1007/s40262-023-01328-1","DOIUrl":"10.1007/s40262-023-01328-1","url":null,"abstract":"<p><strong>Background and objective: </strong>Lenacapavir (LEN) is a novel, first-in-class, multistage, selective inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function recently approved for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. The purpose of this multicohort study was to evaluate the pharmacokinetics, metabolism, excretion, safety, and tolerability of LEN following a single intravenous (IV) infusion of 10 mg LEN or 20 mg [¹⁴C]LEN in healthy participants.</p><p><strong>Methods: </strong>Twenty-one healthy adult participants were enrolled into the study and received either a single IV dose of 10 mg LEN (n = 8 active, n = 3 placebo; cohort 1) or a single IV dose of 20 mg [¹⁴C]LEN containing 200 µCi (n = 10; cohort 2). Blood, urine, and feces samples (when applicable) were collected after dosing, and radioactivity (cohort 2) was assessed using liquid scintillation counting in both plasma and excreta. LEN in plasma was quantified by liquid chromatography (LC) tandem mass spectroscopy (MS/MS) method bioanalysis. Metabolite profiling in plasma and excreta were performed using LC-fraction collect (FC)-high-resolution MS and LC-FC-accelerator mass spectrometry in plasma.</p><p><strong>Results: </strong>Between the 10 mg and 20 mg doses of LEN, the observed plasma exposure of LEN doubled, while the elimination half-life was similar. Following administration of 20 mg [¹⁴C]LEN (200 µCi), the mean cumulative recovery of [¹⁴C] radioactivity was 75.9% and 0.24% from feces and urine, respectively. The mean whole [¹⁴C] blood-to-plasma concentration ratio was 0.5-0.7, which showed a low distribution of LEN to red blood cells. Intact LEN was the predominant circulating species in plasma (representing 68.8% of circulating radioactivity), and no single metabolite contributed to > 10% of total radioactivity exposure through 1176 h postdose. Similarly, intact LEN was the most abundant component (32.9% of administered dose; 75.9% of recovered dose) measured in feces, with metabolites accounting for trace amounts. These results suggest metabolism of LEN is not a primary pathway of elimination. Of the metabolites observed in the feces, the three most abundant metabolites were direct phase 2 conjugates (glucuronide, hexose, and pentose conjugates), with additional metabolites formed to a lesser extent via other pathways. The administered LEN IV doses were generally safe and well-tolerated across participants in this study.</p><p><strong>Conclusions: </strong>The results of this mass balance study indicated that LEN was majorly eliminated as intact LEN via the feces. The renal pathway played a minor role in LEN elimination (0.24%). In addition, no major circulating metabolites in plasma or feces were found, indicating minimal metabolism of LEN.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485267","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 Pharmacokinetic Modeling of Cotadutide: A Dual Agonist Peptide of Glucagon-Like Peptide and Glucagon Receptors Administered to Participants with Type II Diabetes Mellitus, Chronic Kidney Disease, Obesity and Non-Alcoholic Steatohepatitis.","authors":"Hongtao Yu, Magnus Åstrand, Jenny Cheng, Kaila Nitin, Bengt Hamrén, Anis A Khan","doi":"10.1007/s40262-023-01337-0","DOIUrl":"10.1007/s40262-023-01337-0","url":null,"abstract":"<p><strong>Background: </strong>Cotadutide is a dual glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptor agonist peptide. The objective of this analysis was to develop a population pharmacokinetic (popPK) model of cotadutide, and to identify any potential effect on the PK from intrinsic and extrinsic covariates.</p><p><strong>Methods: </strong>The popPK analysis utilized a non-linear mixed-effects modeling approach using the data from 10 clinical studies in different participant categories following once-daily subcutaneous dose administration ranging from 20 to 600 μg. Additionally, the covariates affecting cotadutide exposure were quantified, and the model performance was evaluated through the prediction-corrected visual predictive checks.</p><p><strong>Results: </strong>A one-compartment model with first-order absorption and elimination adequately described the data as confirmed via visual predictive check plots and parameter plausibility. The mean values for cotadutide apparent clearance (CL/F), apparent volume of distribution (V/F), absorption rate constant (Ka), and half-life were 1.05 L/h, 20.0 L, 0.38 h^-1, and 13.3 hours, respectively. Covariate modeling identified body weight, alanine transaminase, albumin, anti-drug antibody (ADA) titer values, formulation strength and injection device, and participant categories as significant covariates on PK parameters, where ADAs have been identified to decrease cotadutide clearance. The model demonstrated that a 150-kg participant was estimated to have 30% lower for both AUC and C_max and a 66 kg participant was estimated to have 35% higher for both AUC and C_max relative to a reference individual with a median weight of 96 kg.</p><p><strong>Conclusions: </strong>A popPK model was developed for cotadutide with cotadutide clinical data, and the impact of the statistically significant covariates identified was not considered clinically meaningful. The popPK model will be used to evaluate exposure-response relationships for cotadutide clinical data.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485269","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":"Factors Influencing Unfractionated Heparin Pharmacokinetics and Pharmacodynamics During a Cardiopulmonary Bypass.","authors":"Audrick Gibert, Julien Lanoiselée, Isabelle Gouin-Thibault, Adeline Pontis, Kasra Azarnoush, Andranik Petrosyan, Nathalie Grand, Serge Molliex, Jérome Morel, Laurent Gergelé, Sophie Hodin, Valérie Bin, Robin Chaux, Xavier Delavenne, Edouard Ollier","doi":"10.1007/s40262-023-01334-3","DOIUrl":"10.1007/s40262-023-01334-3","url":null,"abstract":"<p><strong>Background: </strong>Unfractionated heparin (UFH) is commonly used during cardiac surgery with a cardiopulmonary bypass to prevent blood clotting. However, empirical administration of UFH leads to variable responses. Pharmacokinetic and pharmacodynamic modeling can be used to optimize UFH dosing and perform real-time individualization. In previous studies, many factors that could influence UFH pharmacokinetics/pharmacodynamics had not been taken into account such as hemodilution or the type of UFH. Few covariates were identified probably owing to a lack of statistical power. This study aims to address these limitations through a meta-analysis of individual data from two studies.</p><p><strong>Methods: </strong>An individual patient data meta-analysis was conducted using data from two single-center prospective observational studies, where different UFH types were used for anticoagulation. A pharmacodynamic/pharmacodynamic model of UFH was developed using a non-linear mixed-effects approach. Time-varying covariates such as hemodilution and fluid infusions during a cardiopulmonary bypass were considered.</p><p><strong>Results: </strong>Activities of UFH's anti-activated factor/anti-thrombin were best described by a two-compartment model. Unfractionated heparin clearance was influenced by body weight and the specific UFH type. Volume of distribution was influenced by body weight and pre-operative fibrinogen levels. Pharmacodynamic data followed a log-linear model, accounting for the effect of hemodilution and the pre-operative fibrinogen level. Equations were derived from the model to personalize UFH dosing based on the targeted activated clotting time level and patient covariates.</p><p><strong>Conclusions: </strong>The population model effectively characterized UFH's pharmacokinetics/pharmacodynamics in cardiopulmonary bypass patients. This meta-analysis incorporated new covariates related to UFH's pharmacokinetics/pharmacodynamics, enabling personalized dosing regimens. The proposed model holds potential for individualization using a Bayesian estimation.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086119","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 Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Moderate-to-Severe Psoriasis.","authors":"Jonathan Greenzaid, Steven Feldman","doi":"10.1007/s40262-023-01341-4","DOIUrl":"10.1007/s40262-023-01341-4","url":null,"abstract":"<p><p>Psoriasis is a common inflammatory immune disorder due to chronic activation of the adaptive and innate immune responses. Therapies for psoriasis target reducing inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-17, and interleukin-22. Patients with inflammatory disorders have reduced metabolism by cytochrome P450 enzymes in the liver. The pharmacokinetic and pharmacodynamic changes due to psoriasis also have an impact on reaching therapeutic concentrations of the drug. Pharmacokinetic and pharmacodynamic data help determine the safety and clinical considerations necessary when utilizing drugs for plaque psoriasis. A literature search was performed on PubMed and Ovid MEDLINE for the pharmacokinetic and pharmacodynamic data of oral therapies and biologics utilized for moderate-to-severe plaque psoriasis. The findings from the literature search were organized into two sections: oral therapies and biologics. The pharmacokinetic and pharmacodynamic parameters in healthy patients, patients with psoriasis, and special populations are discussed in each section. The oral therapies described in this review include methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib. Biologics include tumor necrosis factor-alpha inhibitors, interleukin-17 inhibitors, ustekinumab, and interleukin-23 inhibitors. Clinical considerations for these therapies include drug toxicities, dosing frequency, and anti-drug antibodies. Methotrexate and cyclosporine have a risk for hepatoxicity and renal impairment, respectively. Moreover, drugs metabolized via cytochrome P450, including tofacitinib and apremilast have decreased clearance in patients with psoriasis, requiring dose adjustments. Patients treated with therapies such as adalimumab can develop anti-drug antibodies that reduce the long-term efficacy of the drug. Additionally, overweight patients benefit from more frequent dosing to achieve better psoriasis clearance.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569470","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":"Toward Model-Based Informed Precision Dosing of Vancomycin in Hematologic Cancer Patients: A First Step.","authors":"Jessica Le Blanc, Denis Projean, Sandra Savignac, Sophie Léveillé, Marie-Pier Ducas, Annie Brisebois-Boyer, Amélie Marsot","doi":"10.1007/s40262-023-01329-0","DOIUrl":"10.1007/s40262-023-01329-0","url":null,"abstract":"<p><strong>Background and objective: </strong>There is no consensus on the optimal vancomycin dose to achieve pharmacokinetic/pharmacodynamic (PK/PD) target in patients with hematologic cancer or in hematopoietic stem cell transplant (HSCT) recipients. A 24-h area under the concentration-time curve (AUC) >400 mg*h/L must be achieved early for successful treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections. Current nomograms derived from general population data are not sufficiently accurate to allow AUC-based model-informed precision dosing. The objective of this study was to characterize vancomycin PK in patients with hematologic cancer or in HSCT recipients and to develop a model-informed dosing tool based on PK/PD target requirements.</p><p><strong>Methods: </strong>Pooled retrospective and prospective vancomycin serum concentrations were analyzed using NONMEM^® to evaluate the performance of previously published population PK (popPK) models built from hematologic cancer datasets and to develop a novel Bayesian PK model. Patients' characteristics and clinical data were tested as potential covariates. The popPK model was validated internally and externally. Predictions of vancomycin concentrations for different dosing regimens were made using Monte-Carlo simulations, and a nomogram strategy was proposed according to selected probability of target attainment (PTA).</p><p><strong>Results: </strong>The predictive performance of the published popPK models was found to be suboptimal for our population. A novel popPK model was developed using 240 vancomycin concentrations (60 patients). A two-compartment structural model with an additive error model best described the data. Ideal body weight and estimated glomerular filtration rate (eGFR) [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] were selected as covariates for volume of distribution (V) and clearance (CL). Bootstrapping confirmed the stability and precision of the popPK parameters. The volume of distribution was V1 = 46.8 L and V2 = 56.1 L, while CL = 5.63 L/h. External validation using 107 vancomycin concentrations (24 patients) demonstrated the predictivity of the model. A nomogram was developed to reach minimally PTA >50% for 400 < AUC < 600 mg*h/L.</p><p><strong>Conclusion: </strong>To our knowledge, this study provides the first model-informed AUC-based strategy in North American hematologic cancer patients with or without HSCT. The resulting nomogram generated provides a simplified approach to improving the accuracy of initial vancomycin dosing in this population.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828463","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, Pharmacodynamics, and Safety of Single Dose HSK7653 Tablets in Chinese Subjects with Normal or Impaired Renal Function.","authors":"Dan Shi, Lin Chen, Gexuan Li, Nan Wu, Fengyi Zhang, Xiaofei Wang, Nan Mu, Xi Chen, Xiangyi Yang, Jia Lu, Yali Lu, Meixia Wang, Dongliang Zhang","doi":"10.1007/s40262-023-01333-4","DOIUrl":"10.1007/s40262-023-01333-4","url":null,"abstract":"<p><strong>Objective: </strong>HSK7653 is a novel, ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, promising for type 2 diabetes mellitus with a dosing regimen of once every 2 weeks. This trial investigates the pharmacokinetics (PKs), pharmacodynamics (PDs),and safety of HSK7653 in outpatients with normal or impaired renal function.</p><p><strong>Methods: </strong>This is a multicenter, open-label, nonrandomized, parallel-controlled phase I clinical study that investigates the pharmacokinetic profiles of HSK7653 after a single oral administration in 42 subjects with mild (n = 8), moderate (n = 10), severe renal impairment (n = 10), and end-stage renal disease (without dialysis, n = 5) compared with matched control subjects with normal renal function (n = 9). Safety was evaluated throughout the study, and the pharmacodynamic effects were assessed on the basis of a DPP-4 inhibition rate.</p><p><strong>Results: </strong>HSK7653 exposure levels including the maximum plasma concentration (C_max), area under the plasma concentration-time curve from zero to last time of quantifiable concentration (AUC_0-t), and area under the plasma concentration-time curve from zero to infinity (AUC_0-inf) showed no significant differences related to the severity of renal impairment. Renal clearance (CL_R) showed a certain downtrend along with the severity of renal impairment. The CL_R of the group with severe renal impairment and the group with end-stage renal disease were basically similar. The DPP-4 inhibition rate-time curve graph was similar among the renal function groups. All groups had favorable safety, and no serious adverse events occurred.</p><p><strong>Conclusions: </strong>HSK7653 is a potent oral DPP-4 inhibitor with a long plasma half-life, supporting a dosing regimen of once every 2 weeks. Impaired renal function does not appear to impact the pharmacokinetic and pharmacodynamic properties of HSK7653 after a single administration in Chinese subjects. HSK7653 is also well tolerated without an increase in adverse events with increasing renal impairment. These results indicate that dose adjustment of HSK7653 may not be required in patients with renal impairment.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05497297.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110785","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":"Reporting Coefficient of Variation for Logit, Box-Cox and Other Non-log-normal Parameters.","authors":"John P Prybylski","doi":"10.1007/s40262-023-01343-2","DOIUrl":"10.1007/s40262-023-01343-2","url":null,"abstract":"","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650378","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}