Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype‐Derived Activity Scores

Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype‐Derived Activity Scores

Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether...

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Veröffentlicht in:CPT: pharmacometrics and systems pharmacology 2020-12, Vol.9 (12), p.678-685
Hauptverfasser: Thomas, Cameron D., Mosley, Scott A., Kim, Sarah, Lingineni, Karthik, El Rouby, Nihal, Langaee, Taimour Y., Gong, Yan, Wang, Danxin, Schmidt, Siegfried O., Binkley, Philip F., Estores, David S., Feng, Kairui, Kim, Hyewon, Kinjo, Minori, Li, Zhichuan, Fang, Lanyan, Chapman, Arlene B., Cooper-DeHoff, Rhonda M., Gums, John G., Hamadeh, Issam S., Zhao, Liang, Schmidt, Stephan, Frye, Reginald F., Johnson, Julie A., Cavallari, Larisa H.
Format: Artikel
Sprache:eng
Schlagworte:
Drug dosages
Drug therapy
Gene expression
Genotype & phenotype
Heart rate
Hypertension
Pharmacodynamics
Pharmacokinetics
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Zusammenfassung:Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S‐metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P 
ISSN:2163-8306
2163-8306
DOI:10.1002/psp4.12563