Comparative pharmacodynamics of olmesartan and azelnidipine in patients with hypertension: A population pharmacokinetic/pharmacodynamic analysis

Yusuke Tanigawara, Kazutaka Yoshihara, Kizuku Kuramoto, Kikuo Arakawa

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The objectives of this study were to identify the factors influencing antihypertensive response to the angiotensin receptor blocker, olmesartan medoxomil, or the calcium channel blocker, azelnidipine, and to discuss the possibility of utilizing them as predictors for drug selection prior to therapy. A two-way crossover study of olmesartan medoxomil and azelnidipine was conducted in 29 patients with mild to moderate essential hypertension. The 24-hour ambulatory blood pressure measurements (ABPM) and plasma drug concentrations were obtained on the first and at the end of each treatment period, and were analyzed using population pharmacokinetic/pharmacodynamic (PK/PD) modeling approach. The population PK/PD models considering circadian variations in baseline blood pressure well described the observed plasma drug concentrations and 24-hour ABPM profiles. Pre-treatment plasma renin activity (PRA) was identified as a significant covariate on the maximum drug effect (Emax) of olmesartan, whereas azelnidpine Emax was independent of patient background characteristics investigated. No patient was found to have a high Emax to one agent who also had a high Emax to the other. In conclusion, the effects of olmesartan medoxomil and azelnidipine were modestly correlated with pharmacokinetic profiles, and the pre-treatment PRA level could be a useful determinant of responsiveness in selecting olmesartan medoxomil and azelnidipine.

Original languageEnglish
Pages (from-to)376-388
Number of pages13
JournalDrug Metabolism And Pharmacokinetics
Volume24
Issue number4
DOIs
Publication statusPublished - 2009 Jan 1

Keywords

  • Antihypertensive agents
  • Azelnidipine
  • Individualization
  • Olmesartan medoxomil
  • Population pharmacokinetics/pharmacodynamics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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