Pharmacokinetic Interaction Among Telmisartan, Amlodipine, and Hydrochlorothiazide After a Single Oral Administration in Healthy Male Subjects

Purpose: Hypertension is a major risk factor for cardiovascular diseases, necessitating hypertension control. Antihypertensive drugs are more potent when administered in combinations of 2 or 3 different classes of drugs. One such therapy includes a combination of an angiotensin receptor blocker, a calcium channel blocker, and a diuretic. The objective of this study was to evaluate the pharmacokinetic interaction among telmisartan, amlodipine, and hydrochlorothiazide. Methods: : A randomized, open-label, 3-period, 6-sequence, 3-treatment, single-dose crossover study was conducted in healthy male subjects. Subjects were randomly assigned to 1 of 6 sequences and one of the following treatments was administered in each period: treatment A, co-administration of one tablet of telmisartan 80 mg and one tablet of amlodipine 10 mg; treatment B, one tablet of hydrochlorothiazide 25 mg alone; and treatment C, co-administration of all 3 investigational products. Serial blood samples were collected up to 144 hours postdose. Plasma drug concentrations were measured by using LC/MS–MS. Pharmacokinetic parameters, including C_max and AUC_0–last, were determined by using noncompartmental analysis. The geometric least squares mean ratios and associated 90% CIs of log-transformed C_max and AUC_0–last for separate administration or co-administration were calculated to evaluate pharmacokinetic interactions. Findings: Twenty-seven subjects completed the study. The geometric least squares mean ratios and 90% CIs of C_max and AUC_0–last were 1.02 (0.85–1.21) and 1.04 (0.97–1.13) for telmisartan; 1.00 (0.95–1.04) and 0.95 (0.91–0.99) for amlodipine; and 0.88 (0.82–0.96) and 0.86 (0.82–0.90) for hydrochlorothiazide, respectively. No serious adverse events were recorded, and all reported adverse events were of mild intensity. Implications: The pharmacokinetic parameters of telmisartan, amlodipine, and hydrochlorothiazide when administered separately or co-administered were compared, and all the parameters met the criteria for pharmacokinetic equivalence. Combination therapy of these 3 drugs had no significant impact on the pharmacokinetic parameters of each drug. (ClinicalTrials.gov