title: Comparative pharmacodynamics of olmesartan and azelnidipine in patients with hypertension: a population pharmacokinetic/pharmacodynamic analysis.
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 (E(max)) of olmesartan, whereas azelnidpine E(max) was independent of patient background characteristics investigated. No patient was found to have a high E(max) to one agent who also had a high E(max) 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.
authors.affiliation: Department of Pharmacy, School of Medicine, Keio University, Tokyo, Japan. tanigawa@sc.itc.keio.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanigawara
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yoshihara
authors.forename: Kizuku
authors.initials: K
authors.lastname: Kuramoto
authors.forename: Kikuo
authors.initials: K
authors.lastname: Arakawa
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002940:Circadian Rhythm / Q000502:physiology; D019411:Clinical Laboratory Techniques; D018592:Cross-Over Studies; D004095:Dihydropyridines / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007093:Imidazoles / Q000493:pharmacokinetics*; D007207:Individuation; D008297:Male; D008875:Middle Aged; D000068557:Olmesartan Medoxomil; D044382:Population Groups; D013777:Tetrazoles / Q000493:pharmacokinetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007093:Imidazoles; D013777:Tetrazoles; D001383:Azetidinecarboxylic Acid; D000068557:Olmesartan Medoxomil; C437965:olmesartan; C061679:azelnidipine