Pharmacokinetics and safety of olmesartan medoxomil in combination with either amlodipine or atenolol compared to respective monotherapies in healthy subjects.
The aim of this study was to investigate any influence on olmesartan plasma pharmacokinetics from amlodipine or atenolol. We analysed pharmacokinetics and safety of olmesartan medoxomil in combination with either amlodipine or atenolol compared to respective monotherapies in two separate studies. In one study, 18 subjects received once daily treatment for 7 days with olmesartan medoxomil 20 mg alone or with amlodipine 5 mg or amlodipine 5 mg alone. In the other study, atenolol 50 mg once daily replaced amlodipine. Concentration vs. time profiles for olmesartan monotherapy were similar to combination therapy. Mean olmesartan AUC(ss,tau) for olmesartan alone and with amlodipine were 2439 and 2388 ng h/mL and for olmesartan alone and with atenolol were 2340 and 2247 ng h/mL. Corresponding olmesartan C(ss,max) values were 465.7 and 439.5 ng/mL for amlodipine, and 447.4 and 423.8 ng/mL for atenolol. Median t(max) values for olmesartan were 1.5 h for each group in each study. Bioequivalence was established for all pharmacokinetic parameters. Lack of significant pharmacokinetic interactions between olmesartan and amlodipine or atenolol provides a basis for combination therapy.
Bolbrinker
Juliane
J
Institute of Clinical Pharmacology and Toxicology, CharitéCentrum für Therapieforschung, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Huber
Matthias
M
Scholze
Jürgen
J
Kreutz
Reinhold
R
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D017311:Amlodipine / Q000493:pharmacokinetics* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001262:Atenolol / Q000493:pharmacokinetics* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D000068557:Olmesartan Medoxomil; D013777:Tetrazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D013810:Therapeutic Equivalency
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D002121:Calcium Channel Blockers; D007093:Imidazoles; D013777:Tetrazoles; D017311:Amlodipine; D001262:Atenolol; D000068557:Olmesartan Medoxomil