Safety of Candesartan, Amlodipine, and Atorvastatin in Combination: Interaction Study in Healthy Subjects

• Published in: Clinical pharmacology in drug development Vol. 10; no. 2; pp. 190 - 197
• Main Authors: Gundlach, Kristina, Wolf, Katharina, Salem, Isam, Randerath, Olaf, Seiler, Dan
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2021
• Subjects: Adolescent; Adult; Amlodipine - administration & dosage; Amlodipine - adverse effects; Amlodipine - pharmacokinetics; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Antihypertensive Agents - pharmacokinetics; Antihypertensives; Area Under Curve; Atorvastatin - administration & dosage; Atorvastatin - adverse effects; Atorvastatin - pharmacokinetics; Benzimidazoles - administration & dosage; Benzimidazoles - adverse effects; Benzimidazoles - pharmacokinetics; Biphenyl Compounds - administration & dosage; Biphenyl Compounds - adverse effects; Biphenyl Compounds - pharmacokinetics; Cholesterol; comedication; Drug Interactions; drug‐drug interaction; dyslipidemia; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; hypertension; Male; Metabolic disorders; Middle Aged; Pharmacokinetics; Prospective Studies; Statins; Tetrazoles - administration & dosage; Tetrazoles - adverse effects; Tetrazoles - pharmacokinetics; Young Adult; pharmacokinetics; comedication; dyslipidemia; drug-drug interaction; hypertension
• ISSN: 2160-763X; 2160-7648; 2160-7648
• DOI: 10.1002/cpdd.787

For efficient cardiovascular risk protection antihypertensive treatment is often combined with cholesterol‐lowering treatment, although solid data of interaction and side effects are missing. This is a prospective, single‐center interaction study conducted in a fixed sequence design at steady state of candesartan, amlodipine, and atorvastatin. Five‐day monotherapy of candesartan 8 mg was followed by 5‐day atorvastatin 40 mg monotherapy and subsequently 9‐day amlodipine 5 mg monotherapy; each treatment separated by washout phases. Immediately after amlodipine monotherapy, all 3 drugs were administered concomitantly for 5 days. Pharmacokinetic parameters as well as safety were assessed. Eighteen healthy subjects enrolled and completed the study. No significant difference in the maximum concentration (Cmax) and the area the under plasma concentration–time curve (AUC) for amlodipine and AUC of atorvastatin was detected following combination versus monotherapy. Cmax of atorvastatin decreased slightly but clinically not relevantly when given in combination. A statistically significant but not below 0.80‐fold decrease between candesartan following combination vs monotherapy was detected for Cmax and AUC. In general, all treatments were well tolerated. Concluding, systemic exposure of candesartan, amlodipine, and atorvastatin is not clinically significantly changed upon coadministration. These data support a fixed‐dose combination of the 3 components for dual cardiovascular risk prevention.