Limited Sampling Strategy for Predicting the Area under Plasma Concentration–Time Curve of Nadolol in Healthy Subjects.
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 b...
| Published in: | Journal of Clinical Pharmacology Vol. 65; no. 5; pp. 621 - 628 |
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| Main Authors: | , , |
| Format: | research tables/charts Journal Article |
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Wiley-Blackwell
May2025
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=184800089&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 184800089 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: May2025 vid: 65 iid: 5 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 184800089 180985300 184800089 184800089 10.1002/jcph.6164 184800089 ppf: 621 ppct: 7 formats: tig: atl: Limited Sampling Strategy for Predicting the Area under Plasma Concentration–Time Curve of Nadolol in Healthy Subjects. aug: au: Misaka, Shingen Maejima, Yuko Shimomura, Kenju affil: Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University School of Medicine, Fukushima, Japan sug: subj: Nadolol Pharmacokinetics Drug Monitoring Methods Volunteer Workers Psychosocial Factors Drug Interactions Evaluation Human Male Female Adolescence Adult Japan In Vivo Studies Models, Biological Drug-Food Interactions Itraconazole Rifampin Grapefruit Multiple Linear Regression Tea Descriptive Statistics Comparative Studies ROC Curve Algorithms Correlation Coefficient Adolescent: 13-18 years Adult: 19-44 years Male Female ab: 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 (AUC0‐∞) of nadolol. Plasma concentration data (Ct) 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 AUC0‐∞ 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 AUC0‐∞ in different doses. The results suggest that the LSS models using three time points allow a reliable prediction of AUC0‐∞ of nadolol in healthy individuals. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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