Journal of Clinical Pharmacology最新文献

{"title":"Severe Impact of Omeprazole Timing on pH-Sensitive Dasatinib Absorption: Unveiling Substantial Drug-Drug Interaction.","authors":"Per Andersson, Magnus Brisander, Charlotta Liljebris, Gérald Jesson, Hans Lennernäs","doi":"10.1002/jcph.6173","DOIUrl":"https://doi.org/10.1002/jcph.6173","url":null,"abstract":"<p><p>The absorption and bioavailability of most tyrosine kinase inhibitors are affected by gastrointestinal pH as they are weak basic lipophilic drugs. Hence, concomitant use of acid reducing agents (ARAs) is frequently restricted. Particularly comedication of crystalline dasatinib (Sprycel) and proton-pump inhibitors (PPIs) should be avoided. Drug-drug interaction (DDI) studies with PPIs report approximately 40%-80% bioavailability reduction of dasatinib. Limitations in the design of these studies do not allow for assessing the near maximum DDI as timing of PPI dosing was either not reported or 22 h prior to dasatinib intake. We conducted a DDI study of crystalline dasatinib and omeprazole in healthy, fasted participants, investigating the impact of PPI comedication on dasatinib plasma exposure at a time point when the near maximum DDI effect is expected. Participants were administered omeprazole (day 2-5) to reach steady state. On day 6, a single dose of crystalline dasatinib was given. Crystalline dasatinib dosing alone on day 1 served as control (single dose). The dosing interval between omeprazole administration and crystalline dasatinib was 10 h (median [range: 9-10 h]). Dasatinib C_max and AUC_0-24 were reduced by 96% and 89% by omeprazole comedication. C_max was 224.6 ± 104.7 ng/mL (mean ± SD) and 8.0 ± 4.5 ng/mL (P < .0001) and AUC_0-24 was 797.6 ± 274.5 and 90.6 ± 38.1 h·ng/mL (P < .0001) without and with omeprazole. T_1/2 was 5.7 ± 1.5 h (mean ± SD) with crystalline dasatinib dosing alone and could not be reliably calculated with comedication. To ensure optimal patient outcome, it is vital to investigate bioavailability of pH-sensitive drugs at the maximal DDI effect of ARAs to understand the worst-case influence for efficient clinical management.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899608","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":"Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5-HT₃ Antagonist Antiemetic Drugs.","authors":"Lauren E Thompson, Avisek Ghimire, Xia Wen, Christine Kim, Cathleen L Doherty, Brian T Buckley, Daniel W Bowles, Cindy L O'Bryant, Edgar A Jaimes, Lauren M Aleksunes, Melanie S Joy","doi":"10.1002/jcph.6177","DOIUrl":"10.1002/jcph.6177","url":null,"abstract":"<p><p>Cisplatin is a platinum-based chemotherapeutic drug used to treat many types of cancer. The aim of this study was to develop a population pharmacokinetic model that incorporates plasma unbound and bound platinum levels. Cancer patients undergoing their first or second cycle of cisplatin-containing chemotherapy (n = 33) were prospectively randomized to receive a 5-hydroxytryptamine (5-HT₃) antagonist (5-HT₃A) antiemetic (ondansetron, granisetron, or palonosetron) followed by blood collection over 10 days. Total and unbound platinum levels were quantified using inductively coupled plasma mass spectrometry. Plasma concentrations of bound and unbound platinum were used to develop a nonlinear mixed-effect pharmacokinetic model in Phoenix NLME (v8.3, Certara Inc.). A stepwise search was used to screen covariates that influenced pharmacokinetic parameters. A compartment for bound platinum was added to a two-compartment unbound platinum model to create a combined platinum model. The volume of the central compartment for unbound platinum (V1_u) was significantly impacted by previous cisplatin exposure and the intercompartmental clearance of unbound platinum (CL2_u) was significantly influenced by concomitant lorazepam use. The models also suggested ondansetron- and granisetron-treated subjects had a 331% and 114% increase, respectively, in circulating exposures to unbound platinum than palonosetron-treated subjects. The results suggest platinum pharmacokinetics are altered by concomitant 5-HT₃A antiemetic use, concomitant lorazepam use, and previous exposure to cisplatin. Ondansetron and granisetron co-treatment increased unbound platinum exposure compared to palonosetron co-treatment, suggesting that palonosetron may be a preferred 5-HT₃A to reduce the risk of cisplatin-induced kidney injury.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878619","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":"Drug-Drug Interaction Potential of Mavacamten with Midazolam: Combined Results from Clinical and Model-Based Studies.","authors":"Samira Merali, Caroline Sychterz, Vidya Perera, Lu Gaohua, Victoria Florea, Bindu Murthy","doi":"10.1002/jcph.6175","DOIUrl":"https://doi.org/10.1002/jcph.6175","url":null,"abstract":"<p><p>Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and could reduce the effectiveness of concomitant drugs that are metabolized by CYP3A4, such as midazolam. This study aimed to determine if repeat doses of mavacamten achieving clinically relevant exposures affected midazolam exposure. This was a single-center, open-label study in healthy participants. Participants received: on day 1, midazolam 5 mg; on days 2-3, mavacamten 25 mg; on days 4-16, mavacamten 15 mg; and on day 17, mavacamten 15 mg and midazolam 5 mg. Plasma concentrations of mavacamten, midazolam, and the midazolam metabolite 1'-hydroxymidazolam were measured. A physiologically based pharmacokinetic (PBPK) model was used to simulate the effect of mavacamten-mediated CYP3A4 induction on midazolam exposure by CYP2C19 phenotype. Thirteen adult participants were enrolled (46.2% were female; mean [SD] age: 34.0 [9.0] years). Compared with midazolam alone, midazolam coadministered with mavacamten decreased the maximum observed plasma concentration (C_max), area under the drug concentration-time curve (AUC) from time zero to infinity (AUC_0-inf), and AUC from time zero to last measurable concentration (AUC_0-last) for midazolam by 7%, 13%, and 24%, respectively; for 1'-hydroxymidazolam, AUC_0-inf and AUC_0-last increased by 20% and 11%, respectively. Ten participants experienced adverse events and the majority were mild in severity. The PBPK model predicted the clinical trial data well. The PBPK simulation assessed that the overall impact of mavacamten on midazolam C_max and AUC was predicted to be weak regardless of CYP2C19 phenotype. At clinically relevant exposures, mavacamten had a negligible effect on midazolam exposure.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847960","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":"Preclinical and Clinical Pharmacokinetics of JNJ-75220795, an siRNA Therapeutic Targeting PNPLA3, for Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Jae Yoon Jeon, Vivaswath S Ayyar, Shohei Ouchi, Elisa Fabbrini, Anastasiya Koshkina, Jeffery J Prusakiewicz, Jed Dallas, Txheng Yang, Wenying Jian, Lijuan Kang, Korin Cofsky, Brian Rady, Ryo Tamamura, Yuki Saito, Aimi Yamashita, Tamisha Vaughan, Susan Wendel, Hideo Makimura, Dénes Csonka, Navin Goyal","doi":"10.1002/jcph.6174","DOIUrl":"https://doi.org/10.1002/jcph.6174","url":null,"abstract":"<p><p>JNJ-75220795 or ARO-PNPLA3 is an investigational small interfering ribonucleic acid agent conjugated with N-acetyl-d-galactosamine that targets the PNPLA3 gene, currently being developed for metabolic dysfunction-associated steatohepatitis (MASH). This study evaluated the pharmacokinetics (PK) profile of single subcutaneous doses of JNJ-75220795 in preclinical species as well as in human subjects with homozygous or heterozygous PNPLA3 I148M mutation in two phase 1 studies-a first-in-human study in the United States and a first-in-Japanese study in Japan. Preclinical PK in rats and non-human primates (NHP) showed a rapid systemic absorption and elimination following single subcutaneous doses. JNJ-75220795 was predominantly distributed to the liver with peak liver concentrations reached at 4 h and still detectable at 672 and 336 h in rats and NHPs, respectively, with an apparent liver-to-plasma area under the curve (AUC) ratio of 2800 in rats. Consistent with the preclinical findings, clinical PK showed rapid systemic absorption and clearance in humans with median peak concentrations at 3.0-9.0 h and mean short half-life of 3.4-6.2 h. Plasma PK exposure parameters including C_max and AUC increased approximately dose proportionally. Kidney had the second highest tissue exposure following the liver in rats. Renal excretion was a significant but minor elimination pathway as approximately 15%-25% of the administered dose was recovered in urine. Based on the overall data, JNJ-75220795 was primarily localized to the liver and exhibited sustained hepatic exposures, which confer prolonged pharmacodynamic effects in the target organ. The favorable PK profiles of single subcutaneous doses observed in the phase 1 studies support continued clinical development of JNJ-75220795 for the treatment of MASH.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802834","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":"The Impact of Survival Benefit and Study Design on FDA Approval for Anticancer Drugs Over the Past Decades.","authors":"Koji Ishizuka, Shunsuke Ono","doi":"10.1002/jcph.6172","DOIUrl":"https://doi.org/10.1002/jcph.6172","url":null,"abstract":"<p><p>Despite the tremendous effort in the oncology community, the success rate of anticancer development remained low at 30% to 40% from the Phase 3 study to the regulatory approval. The factors associated with the regulatory approval for market authorization have gained interest in the community to improve the success rate of drug development. Using the data from 208 Phase 3 studies for anticancer drugs, we explored the possible factors associated with the US Food and Drug Administration's (FDA's) approval by multivariate logistic regression analysis. The model incorporated 21 factors from therapeutic context, study design, and outcomes. The hazard ratio (HR) for overall survival (OS) showed a significant association with FDA approval (coefficient: -29.907, P < .001), and the age of control drugs in the market followed (coefficient: -2.581, P = .008). In the model, if the HR for OS changes from 0.75 to 0.85, the probability of FDA approval remarkably decreases from 79.6% to 16.4%. A 50% likelihood of FDA approval is predicted at HR 0.795 for OS. Furthermore, the P-value for the OS test and the width of the confidence interval on HR for OS showed a significant association with the probability of FDA approval. These findings consistently underscore the rigorous standard required for new anticancer drugs to obtain regulatory approval from the FDA.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802837","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":"Ritonavir may prolong sedation but is unlikely to increase the risk of respiratory arrest in patients requiring intravenous midazolam for procedural sedation.","authors":"Jason Arsanious, Angela Rowland, Michael J Sorich, Ashley M Hopkins, Sam Alfred, Andrew Rowland","doi":"10.1002/jcph.6171","DOIUrl":"https://doi.org/10.1002/jcph.6171","url":null,"abstract":"<p><p>Intravenous midazolam is frequently used for procedural sedation. Use of ritonavir containing antivirals in patients requiring procedural sedation with intravenous midazolam is postulated to increase the risk or prolong the consequences of exposure related adverse events. The primary objective of this study was to characterize interaction of ritonavir with IV midazolam. The secondary objective was to define the time course over with the interaction of ritonavir with IV midazolam resolves following cessation of ritonavir. Physiologically based pharmacokinetic modeling was used to conduct clinical trials with a parallel group design defining exposure to a single 5 mg IV dose of midazolam in the presence and absence of nirmatrelvir/ritonavir dosed twice daily for 5 days. Simulations comprised 50 virtual healthy subjects aged 20 to 50 years (50% female). Based on FDA criteria, a moderate/strong interaction between nirmatrelvir/ritonavir and intravenous midazolam (area under the curve [AUC] ratio >2) was observed when intravenous midazolam was administered up to 72 h following cessation of nirmatrelvir/ritonavir. The geometric mean (90% CI) midazolam AUC ratio was 9.21 (5.44 to 16.43) when coadministered on the final day of nirmatrelvir/ritonavir dosing. Importantly, there was no change in peak exposure; the geometric mean (90% CI) midazolam maximum concentration ratio was 0.99 (0.99 to 1.00). Use of ritonavir containing antivirals is unlikely to increase a patient's risk of experiencing an exposure related adverse event following administration of intravenous midazolam but may prolong complications in patients who experience an event. A meaningful interaction persists for 72 h following cessation of nirmatrelvir/ritonavir.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741072","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 Atorvastatin and Metformin after Coadministration with Islatravir in Healthy Adults.","authors":"Jacqueline B McCrea, Munjal Patel, Yang Liu, Ryan Vargo, Rose Witter, Andrew Litovsky, S Aubrey Stoch, Marian Iwamoto, Randolph P Matthews","doi":"10.1002/jcph.6169","DOIUrl":"https://doi.org/10.1002/jcph.6169","url":null,"abstract":"<p><p>Islatravir, a deoxyadenosine analog that inhibits HIV-1 replication by multiple mechanisms of action, including reverse transcriptase translocation inhibition, is being developed for use in HIV-1 treatment. People living with HIV often have comorbidities, such as dyslipidemia or type 2 diabetes mellitus, necessitating long-term concomitant drug therapy. This nonrandomized, two-period, fixed-sequence, open-label, phase 1, drug-drug interaction study was conducted to evaluate the effects of islatravir coadministration on atorvastatin and metformin pharmacokinetics (PK) in healthy adults. In period 1, participants received a single dose of atorvastatin 20 mg and metformin 1000 mg. After a 5-day washout, participants received atorvastatin 20 mg and metformin 1000 mg coadministered with a single oral dose of islatravir 60 mg (period 2). In both periods, blood samples were collected up to 72 h post dose to characterize the plasma PK of atorvastatin and metformin. Safety was monitored throughout the study. Fourteen participants were enrolled and completed the study. Atorvastatin and metformin plasma PK were similar after administration of atorvastatin and metformin with or without islatravir. The geometric mean ratio and 90% confidence interval of the area under the concentration-time curve from time zero to infinity (AUC_0-∞) for atorvastatin and metformin with or without a single oral dose of islatravir were 1.04 (1.00-1.10) and 0.87 (0.79-0.96), respectively. Coadministration of islatravir with atorvastatin and metformin was well tolerated. Overall, coadministration of atorvastatin and metformin with a single oral dose of islatravir did not have a clinically meaningful effect on the PK profiles of either drug.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717336","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":"Patients in Clinical Trials are Sub-Optimally Protected for Drug-Drug Interactions: A Call for Action.","authors":"David Burger, Loek de Jong, Daphne van Dijk, Catherijne A J Knibbe, Rob Ter Heine, Elise Smolders, Munir Pirmohamed","doi":"10.1002/jcph.6168","DOIUrl":"https://doi.org/10.1002/jcph.6168","url":null,"abstract":"","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683201","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":"Results of the ACTION-Galactosemia Kids Study to Evaluate the Effects of Govorestat in Pediatric Patients with Classic Galactosemia.","authors":"Evan Bailey, Han Phan, Ayesha Ahmad, Janet Thomas, Elizabeth G Ames, Amanda B Pritchard, Shane C Quinonez, Stella Wang, Caleb Dayley, Andrew Salt, Christina Pick, Abe Durrant, Samuel Johnson, Jessie Nicodemus-Johnson, Samuel P Dickson, Riccardo Perfetti, Suzanne B Hendrix, Shoshana Shendelman","doi":"10.1002/jcph.6170","DOIUrl":"https://doi.org/10.1002/jcph.6170","url":null,"abstract":"<p><p>To evaluate the pharmacodynamic effects and clinical outcomes of orally administered once-daily govorestat (AT-007), a central nervous system penetrant aldose reductase inhibitor, the double-blind placebo-controlled ACTION-Galactosemia Kids study (NCT04902781) randomly assigned 47 participants (2-17 years old) with Classic Galactosemia to 18 months of govorestat or placebo (2:1) treatment. Mean change in galactitol was compared between the treatment groups at each post-baseline timepoint using a t-test, with a mixed model for repeated measures (MMRM) analysis as a sensitivity analysis. Changes from baseline in clinical outcomes were compared between treatment groups also using a t-test with two different MMRM models as sensitivity models, one including baseline clinical outcome score. The pharmacodynamic effect of govorestat was assessed by correlating galactitol level at 3 months with change from baseline in clinical measures at 18 months using a Pearson correlation. Govorestat treatment resulted in a rapid and sustained reduction in plasma galactitol. Govorestat treatment stabilized or improved clinical measures of behavior, daily living skills, adaptive skills, cognition, tremor, and fine motor skills, which declined over time in the placebo group. Govorestat treatment did not demonstrate a benefit compared with placebo on speech outcomes or gross motor skills, which improved in both treatment groups over 18 months. Govorestat was safe and well tolerated, with adverse events well balanced between the active and placebo groups. Aldose reductase inhibition with govorestat represents a potential opportunity to lower galactitol and improve clinical outcomes in children with Classic Galactosemia.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683204","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":"Limited Sampling Strategy for Predicting the Area under Plasma Concentration-Time Curve of Nadolol in Healthy Subjects.","authors":"Shingen Misaka, Yuko Maejima, Kenju Shimomura","doi":"10.1002/jcph.6164","DOIUrl":"https://doi.org/10.1002/jcph.6164","url":null,"abstract":"<p><p>Nadolol is a hydrophilic β-adrenoceptor blocker with a relatively long half-life and negligible metabolism. It is a substrate of P-glycoprotein and organic anion transporting polypeptide 1A2, and may serve as an in vivo probe drug for the assessment of drug-drug and food-drug interactions mediated by these transporters. In the present study, we aimed to develop limited sampling strategy (LSS) models for predicting the area under the plasma concentration-time curve (AUC_0-∞) of nadolol. Plasma concentration data (C_t) in healthy volunteers reported in four previous studies were randomly divided into a training dataset for model development (n = 15) and a test dataset for model validation (n = 16). By multiple linear regression analysis, we confirmed that four out of the eight models using two time points and all models using three time points met the acceptable criteria. In particular, the three time point models using (C₃, C₆, and C₂₄) and (C₄, C₈, and C₂₄) showed better predictive performances with r² values of 0.983 and 0.980, respectively. In drug interaction studies of nadolol with itraconazole, rifampicin, grapefruit juice, and green tea extract, both LSS models accurately predicted the AUC_0-∞ with percent mean absolute error ≤11% and percent root mean square error ≤12%. In addition, using digitized pharmacokinetic data of nadolol, both LSS models were further validated by predicting the AUC_0-∞ in different doses. The results suggest that the LSS models using three time points allow a reliable prediction of AUC_0-∞ of nadolol in healthy individuals.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649022","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}