Journal of Clinical Pharmacology最新文献

{"title":"Subclinical Hyperthyroidism Enhances Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women.","authors":"Robert Krysiak, Karolina Kowalcze, Bogusław Okopień","doi":"10.1002/jcph.6144","DOIUrl":"https://doi.org/10.1002/jcph.6144","url":null,"abstract":"<p><p>Metformin treatment decreases elevated concentrations of anterior pituitary hormones. The aim of this prospective, cohort study was to investigate whether hyperthyroidism modulates the impact of metformin on gonadotroph secretory function. The study population included 48 postmenopausal women with untreated type 2 diabetes or prediabetes, 24 of whom had coexisting grade 1 subclinical hyperthyroidism. Both groups were matched for age, insulin sensitivity, and gonadotropin levels. Over the entire study period, all participants were treated with metformin (2.55-3 g daily). Plasma glucose, insulin, thyroid-stimulating hormone (TSH), total and free thyroid hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, adrenocorticotropic hormone (ACTH), and insulin-like growth factor-1 (IGF-1) were assayed at entry and 6 months later. At baseline, the study groups differed in levels of TSH and thyroid hormones but not in body mass index, blood pressure, glucose homeostasis markers (fasting glucose, homeostatic model assessment 1 of insulin resistance ratio [HOMA1-IR], and glycated hemoglobin [HbA_1c]), and the remaining hormones. There were no differences between both groups in the degree of reduction in plasma glucose and HbA_1c in response to metformin treatment. Although metformin decreased HOMA1-IR in both groups, this effect was stronger in women with hyperthyroidism than with normal thyroid function (-50 ± 20% vs -30 ± 15%). Similar relationships were observed for FSH (-43 ± 21% vs -21 ± 12%). Only in hyperthyroid women did the drug reduce LH concentration (by 35 ± 17%). Metformin did not affect circulating levels of TSH, total and free thyroxine, total and free triiodothyronine, estradiol, prolactin, ACTH, and IGF-1. The obtained results indicate that hyperthyroidism enhances the gonadotropin-lowering effects of metformin, as well as the fact that this agent has a neutral effect on the hypothalamic-pituitary-thyroid axis in case of its overactivity.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373316","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":"Pharmacodynamic Exposure-Response Analysis of Fracture Count Data Following Treatment with Burosumab in Patients with XLH.","authors":"Krina Mehta, Jose Storopoli, Nikita Ramwani, Emilia Quattrocchi, Joga Gobburu, Thomas Weber, Matthew W Hruska, Douglas Marsteller","doi":"10.1002/jcph.6140","DOIUrl":"https://doi.org/10.1002/jcph.6140","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is a rare genetic disorder caused by excessive fibroblast growth factor 23 (FGF23), leading to low serum phosphate levels resulting in increased risk of fractures and pseudofractures. Burosumab is indicated for the treatment of XLH. In this work, we aimed to understand the quantitative relationship between burosumab-treatment-induced improvements in serum phosphate and reduction in fracture and pseudofracture counts in adults with XLH. Burosumab pharmacokinetic pharmacodynamic data from nine clinical studies were first utilized to update a prior population pharmacokinetic pharmacodynamic (PPKPD) model. The updated PPKPD model predictions for serum phosphate exposures along with other factors (i.e., time and treatment) were utilized to evaluate the relationship on fracture counts using Poisson model. The updated PPKPD model suggested that burosumab concentrations required for 50% of maximal effect decreased with increasing baseline serum phosphate levels. A Poisson model with time from baseline, average serum phosphate, and burosumab treatment described the time-varying fracture and pseudofracture count data appropriately. The model suggested a baseline rate of fracture and pseudofracture of 1.87 counts. The model predicted that fracture counts decrease by 1% each week, and by 23% with each unit increase (1.0 mg/dL) in average serum phosphate from lower limit of normal (2.5 mg/dL). An additional 1% decrease in fracture count each week was attributed to burosumab treatment that could not be explained by improvements in serum phosphate. Overall, the model quantified the relationship between burosumab-treatment-induced serum phosphate improvements and reduction in fracture and pseudofracture counts in patients with XLH over time.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330510","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":"Time Course of Reversal of Fentanyl-Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene and Intramuscular and Intranasal Naloxone.","authors":"Alessandra Cipriano, Glen Apseloff, Ram P Kapil, Ellie He, Manjunath Shet, Stephen C Harris","doi":"10.1002/jcph.6132","DOIUrl":"https://doi.org/10.1002/jcph.6132","url":null,"abstract":"<p><p>The increase in opioid overdose deaths, particularly involving potent, long-acting synthetic opioids, has led to calls for stronger, longer-acting opioid-overdose-reversal agents. Using an opioid-induced respiratory depression model, we investigated the onset and time course of action of naloxone and a long-acting opioid antagonist, nalmefene, in reversing the effects of an ongoing intravenous fentanyl infusion over a period of up to 100 min. Healthy, moderately experienced opioid users received intramuscular (IM) nalmefene 1 mg, IM naloxone 2 mg, or intranasal (IN) naloxone 4 mg after fentanyl-induced respiratory depression was established based on reduction in respiratory minute volume (MV). Each participant received each opioid antagonist twice per a randomized crossover schedule. Reversal of respiratory depression, pharmacokinetics, and safety were investigated. Participants showed rapid increases in plasma opioid antagonist concentrations, and meaningful reversal of depressed MV tended to occur earlier with IM nalmefene and IM naloxone than with IN naloxone. Compared to naloxone, nalmefene provided extended exposure, and mean MV was maintained at a higher level. All participants experienced treatment-related adverse events, but none were severe, serious, or led to study drug discontinuation. This study provides evidence that IM nalmefene 1 mg achieves reversal of fentanyl-induced respiratory depression similar to or better than that achieved with standard-of-care naloxone treatments. No new safety concerns were raised for IM nalmefene at the tested dose. The pharmacokinetic and pharmacodynamic properties of IM nalmefene position it as an important treatment option in opioid overdose reversal, particularly given the increasing prevalence of overdoses involving potent, long-acting synthetic opioids.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330512","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 of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study.","authors":"Ramachandra Sangana, Bernhards Ogutu, Adoke Yeka, Sylvia Kusemererwa, Halidou Tinto, Andre Offianan Toure, Afizi Kibuuka, Moussa Lingani, Carlos Lourenço, Ghyslain Mombo-Ngoma, Videlis Nduba, Tiacoh Landry N'Guessan, Guétawendé Job Wilfried Nassa, Mary Nyantaro, Lucas Otieno Tina, Anup Anvikar, Abhinav Sinha, Grace Kaguthi, Bakary Fofana, Martin Peter Grobusch, Myriam El Gaaloul, Anne Claire Marrast, Rashidkhan Pathan, Havana Chikoto, Katalin Csermak, Celine Risterucci, Guoqin Su, Cornelis Winnips, Jie Zhang, Julia Zack","doi":"10.1002/jcph.6138","DOIUrl":"https://doi.org/10.1002/jcph.6138","url":null,"abstract":"<p><p>The novel antimalarial ganaplacide combined with lumefantrine solid dispersion formulation (LUM-SDF) was effective and well tolerated in the treatment of uncomplicated falciparum malaria in adults, adolescents, and children in a multinational, prospective, randomized, active-controlled Phase II study conducted between August 2017 and June 2021 (EudraCT 2020-003284-25, Clinicaltrials.gov NCT03167242). Pharmacokinetic data from that study are reported here. The trial comprised three parts: a run-in part in 12 adult/adolescent patients treated with a single dose of ganaplacide 200 mg plus LUM-SDF 960 mg assessed potential pharmacokinetic (PK) interactions between ganaplacide and lumefantrine; in Part A, adult/adolescent patients received one of the six ganaplacide-LUM-SDF regimens or artemether-lumefantrine; and in Part B, three dose regimens identified in Part A, and artemether-lumefantrine, were assessed in children aged 2 to <12 years, with body weight ≥10 kg. A rich blood sampling schedule was used for all 12 patients in the PK run-in part and a subset of patients (N = 32) in Part A, with sparse sampling for remaining patients in Parts A (N = 275) and B (N = 159). Drug concentrations were determined by a validated protein precipitation and reverse phase liquid chromatography with tandem mass spectrometry detection method. Parameters including AUC_inf, AUC_last, AUC_0-t, C_max, and t_max were reported where possible, using non-compartmental analysis. In the PK run-in part, there was no notable increase in ganaplacide or lumefantrine exposure when co-administered. In Parts A and B, ganaplacide exposures increased with dose, but lumefantrine exposure was numerically under dose-proportional. Lumefantrine exposure was higher with ganaplacide-LUM-SDF than with artemether-lumefantrine, although high variability was observed. Ganaplacide and lumefantrine exposures (C_max and AUC_{0-24 h}) were comparable across age and body weight groups. Drug exposures needed for efficacy were achieved using the dose regimen 400 mg ganaplacide plus lumefantrine 960 mg once daily for 3 days under fasted conditions.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330511","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":"Determination of Vatiquinone Drug-Drug Interactions, as CYP450 Perpetrator and Victim, Using Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation.","authors":"Lucy Lee, Noriko Okudaira, Katsuyuki Murase, Ronald Kong, Hannah M Jones","doi":"10.1002/jcph.6133","DOIUrl":"https://doi.org/10.1002/jcph.6133","url":null,"abstract":"<p><p>Vatiquinone, a 15-lipoxygenase inhibitor, is in development for patients with Friedreich's ataxia. Physiologically based pharmacokinetic (PBPK) modeling addressed drug-drug interaction gaps without additional studies. A PBPK model (Simcyp Simulator version 21, full model) was developed using parameters obtained from in vitro studies, in silico estimation and optimization, and two clinical studies. A venous blood dosing model best characterized vatiquinone lymphatic absorption. Apparent oral clearance (CL/F) was used to optimize intrinsic clearance (CL_int). Intestinal availability (F_g) was estimated using the hybrid flow term (Q_gut), unbound fraction in the enterocytes (fu_gut), and gut intrinsic metabolic clearance (CLu_G,int). Renal clearance (CL_R) was set to zero. Assuming an F_a of 1, CYP3A4 contribution (fm_CYP3A4) was further optimized. The PBPK model was verified with two clinical studies and demonstrated that it adequately characterized vatiquinone PK. As a perpetrator, the model predicted no risk for vatiquinone to significantly alter the drug exposures of CYP3A4 and CYP1A2 substrates as evident bynegligible reduction in both midazolam and caffeine area under the curve (AUC)_inf and C_max. As a victim, the model predicted that vatiquinone exposures are weakly influenced by moderate CYP3A4 inhibitors and inducers. With fluconazole coadministration, vatiquinone AUC_inf and C_max increased by nearly 50% and 25%, respectively. With efavirenz coadministration, vatiquinone AUC_inf and C_max decreased by approximately 20% and 10%, respectively. Results suggested that vatiquinone does not significantly impact CYP3A4 and CYP1A2 substrates and that moderate CYP3A4 inhibitors and inducers weakly impact vatiquinone AUC.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299274","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":"Ensuring the Appropriate Use of Glucagon-Like Peptide-1 Receptor Agonists.","authors":"Kenneth Todd Moore, Aman Gupta, Jinshan Shen, Parag Kumar","doi":"10.1002/jcph.6136","DOIUrl":"https://doi.org/10.1002/jcph.6136","url":null,"abstract":"","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299275","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":"Incidence of Acute Kidney Injury in Trough and AUC/MIC Vancomycin Dosing Strategies in a Large Tertiary Care Center: A Retrospective Cohort.","authors":"Rafael Ruiz-Gaviria, Sarah J Norman, Sarah H Elgendi, Jiling Chou, Sheena Ramdeen","doi":"10.1002/jcph.6130","DOIUrl":"https://doi.org/10.1002/jcph.6130","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a complication associated with vancomycin use. There is evidence that this was related to the presence of supratherapeutic vancomycin levels rather than the drug itself. The area under the curve over 24 h to minimum inhibitory concentration (AUC/MIC) dosing for vancomycin has replaced trough-based dosing, but the impact of this change on AKI rates remains unclear. A retrospective cohort study was conducted in a tertiary care teaching hospital. Patients from the trough cohort were recruited from January 1, 2019, to June 30, 2019, and the AUC/MIC cohort from July 1, 2021, to January 1, 2022. Sociodemographics, clinical characteristics, and concomitant medications were obtained. AKI was defined by The Kidney Disease Improving Global Outcomes. A total of 1056 patients were included, 509 in the trough cohort and 547 in the AUC/MIC cohort. The baseline rates of chronic kidney disease were 15.4% and 9.9%, respectively. The AKI rates were 15.9% and 11.9% for trough and AUC/MIC cohorts, respectively (P-value .045). The most frequent nephrotoxins were piperacillin/tazobactam (TZP), diuretics, and IV contrast for both groups. The rates of supratherapeutic levels were higher in the trough cohort (20.7%) than in the AUC/MIC cohort (6.6%). The multivariate logistic regression analysis showed that trough dosing was not associated with increased rates of AKI (OR = 0.96 CI 0.64-1.44). Supratherapeutic levels (OR = 4.64), diuretics (OR = 1.62), TZP (OR = 2.01), and ICU admission (OR = 1.72) were associated with AKI. Vancomycin AUC/MIC dosing strategy was associated with decreased rates of supratherapeutic levels of this drug compared to trough dosing, with a trend toward lower rates of AKI.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134272","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":"A Model-Based Approach Supporting Abacavir/Dolutegravir/Lamivudine Fixed-Dose Combination Approval in Children Living with HIV-1.","authors":"Hardik Chandasana, Ann M Buchanan, Michael McKenna, Cindy Brothers, Stephen Hyatt, Kimberly Adkison, Navin Goyal, Lionel K Tan","doi":"10.1002/jcph.6128","DOIUrl":"https://doi.org/10.1002/jcph.6128","url":null,"abstract":"<p><p>In March 2022, the US Food and Drug Administration expanded indications of TRIUMEQ, a once-daily fixed-dose combination (FDC) containing abacavir (ABC), dolutegravir (DTG), and lamivudine (3TC) to include pediatric patients weighing at least 10 kg for the treatment of HIV-1. Prior to this extension, the ABC 600 mg/DTG 50 mg/3TC 300 mg FDC tablet was approved for use only in the adult/adolescent population, weighing ≥40 kg while each component of the FDC was approved for its use in pediatric patients at least 3 months and older. A new child-friendly formulation was developed as an FDC dispersible tablet (DT) of ABC 60 mg/DTG 5 mg/3TC 30 mg for pediatric patients with a body weight ≥ 6 kg. The present work demonstrates the utility of applying a model-informed drug development (MIDD) approach to expedite ABC/DTG/3TC FDC approval for pediatric patients (≥10 to <40 kg) based on data from the existing individual components and formulation bridging. Population pharmacokinetic models developed for pediatric participants across all three components of ABC/DTG/3TC FDC were employed for exposure prediction and incorporated relative bioavailability data. The predicted plasma exposures of ABC, DTG, and 3TC for FDC doses were consistent with those observed for the single entities in pediatric and adult studies. Thus, safety and efficacy observed in the individual component studies could be adequately extrapolated to the FDC that results in similar exposure. The current work demonstrates the significance of MIDD approaches in facilitating expedited access to child-friendly formulations in the HIV-1 therapeutic area.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134271","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":"Efficacy of Low-Dose Scopolamine and Palonosetron in Reducing Immediate Post-Gastrointestinal Endoscopy Nausea and Vomiting: A Prospective, Randomized, Controlled Study.","authors":"Jianghuai Lin, Zhiming Cai, Yingzi Lin, Huanghui Wu, Yu Gu","doi":"10.1002/jcph.6127","DOIUrl":"https://doi.org/10.1002/jcph.6127","url":null,"abstract":"<p><p>This study aimed to assess the incidence of post-discharge nausea and vomiting (PDNV) following sedation with nalbuphine and etomidate and to evaluate the prophylactic effects of scopolamine in reducing PDNV. A two-stage prospective clinical trial was conducted. The first part involved an observational study of 77 subjects to assess the PDNV incidence post-sedation with nalbuphine, etomidate, and propofol. The second part compared the effectiveness of palonosetron 0.075 mg (P group), scopolamine 0.1 mg (S group), and their combination (PS group) in reducing PDNV. The primary endpoint was the incidence of PDNV within 8 h post-sedation. Secondary outcomes included PDNV frequency and severity at 8-24, 0-24, and 24-48 h and side effects of medications. The incidence of PDNV within 8 h post-sedation was 37.66% (29/77). The PS group showed a significantly lower PDNV rate of 2.56% within 8 h, compared to the P group (35.71%, P < .001), S group (19.64%, P < .001), and control group (38.39%, P < .001), respectively. The S group (19.64%) also had a lower rate than the P group (35.71%, P = .007) and the control group (38.39%, P = .002). Subgroup analysis suggested a potential differential effect of palonosetron in reducing vomiting among male patients undergoing gastrointestinal procedures. The combination therapy was also associated with fewer cases of mild or no nausea and vomiting. In summary, the incidence of PDNV following sedation with nalbuphine and etomidate was notably high. The combination of scopolamine and palonosetron was more effective in preventing PDNV, with implications for improved post-sedation care.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120915","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 of Vancomycin and its Comparison with Population Pharmacokinetic Model in Neonates.","authors":"Ailing Cao, Qiaoxi Li, Minzhen Han, Qian Liu, Heng Liang, Lu Tan, Yanping Guan","doi":"10.1002/jcph.6126","DOIUrl":"https://doi.org/10.1002/jcph.6126","url":null,"abstract":"<p><p>Vancomycin has a narrow therapeutic window and a high inter-individual pharmacokinetic variability, especially in neonates with fast maturational and pathophysiological changes, that needs individualized dosing. Physiologically based pharmacokinetic (PBPK) model and population pharmacokinetic (PopPK) model are both useful tools in model-informed precision dosing, while the former is under research in application of vancomycin in neonates. This study aimed to develop a PBPK model of vancomycin in adult and pediatric population, and compared it with published PopPK model (priori or Bayesian method) in predicting vancomycin concentration in 230 neonatal patients (postmenstrual age, PMA, 25-45 weeks). The developed PBPK model showed a good fit between predictions and observations. PBPK model and PopPK model are complementary in different clinical scenarios of vancomycin application. The physiological-change description of PBPK model showed a superior advantage in initial dosing optimization. As for subsequent dose optimization, PopPK Bayesian forecasting performed better than the PBPK estimation in neonates. However, initial precision dosing tools for early neonates (with PMA < 36 weeks) still need further exploitation.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120916","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}