The Utility of a Population Approach in Drug-Drug Interaction Assessments: A Simulation Evaluation.
This study aims at evaluating the utility of the population pharmacokinetics approach in therapeutic protein drug-drug-interaction (DDI) assessment. Simulations were conducted for 2 representative victim drugs, methotrexate and trastuzumab, using a parallel-group design with and without the interact...
| Publicado en: | Journal of Clinical Pharmacology Vol. 57; no. 10; pp. 1268 - 1279 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Oct2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=125841943&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 125841943 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Oct2017 vid: 57 iid: 10 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 125841943 125841943 125841943 10.1002/jcph.921 125841943 ppf: 1268 ppct: 11 formats: tig: atl: The Utility of a Population Approach in Drug-Drug Interaction Assessments: A Simulation Evaluation. aug: au: Wang, Diane D. Yu, Yanke Kassir, Nastya Zhu, Min Hanley, William D. Earp, Justin C. Chow, Andrew T. Gupta, Manish Hu, Chuanpu affil: Pfizer, La Jolla CA, USA sug: subj: Drug Interactions Methotrexate Pharmacokinetics Trastuzumab Pharmacokinetics Proteins Pharmacokinetics Human Simulations Population Characteristics Confidence Intervals Comparative Studies ab: This study aims at evaluating the utility of the population pharmacokinetics approach in therapeutic protein drug-drug-interaction (DDI) assessment. Simulations were conducted for 2 representative victim drugs, methotrexate and trastuzumab, using a parallel-group design with and without the interaction drug. The effect of a perpetrator on the exposure of the victim drug is described as the ratio of clearance/apparent clearance of the victim drug given with or without the perpetrator. The power of DDI assessment was calculated as the percentage of runs with 90% confidence interval of the estimated DDI effect within 80% to 125% for the scenarios of no DDI, benchmarked with the noncompartmental approach with intensive sampling. The impact of the number of subjects, the number of sampling points per subject, sampling time error, and model misspecification on the power of DDI determination were evaluated. Results showed that with equal numbers of subjects in each arm, the population pharmacokinetics approach with sparse sampling may need about the same or a higher number of subjects compared to a noncompartmental approach in order to achieve similar power. Increasing the number of subjects, even if only in the study drug alone arm, can increase the power. Sampling or dosing time error had notable impacts on the power for methotrexate but not for trastuzumab. Model misspecification had no notable impacts on the power for trastuzumab. Overall, the population pharmacokinetics approach with sparse sampling built in phase 2/3 studies allows appropriate DDI assessment with adequate study design and analysis and can be considered as an alternative to dedicated DDI studies. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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