Tags

Type your tag names separated by a space and hit enter

Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study.
Clin Ther. 2016 Aug; 38(8):1845-57.CT

Abstract

PURPOSE

Rosuvastatin, a hydroxy methylglutaryl coenzyme A reductase inhibitor; telmisartan, an angiotensin receptor blocker; and amlodipine, a calcium channel inhibitor, are commonly prescribed together for the treatment of hypertension nonresponsive to monotherapy and accompanied by dyslipidemia. However, the pharmacokinetic interactions among these 3 substances are not well understood. The aim of this study was to investigate the pharmacokinetic drug-drug interactions among rosuvastatin, telmisartan, and amlodipine in a healthy Korean male population.

METHODS

In both parts of this randomized, open-label, multiple-dose, 2-part, 2-period crossover study, subjects aged 19 to 55 years were enrolled. In part 1, each subject received rosuvastatin 20 mg with and without 2 fixed-dose combination (FDC) tablets of telmisartan/amlodipine 40/5 mg, once daily for 9 consecutive days. In part 2, each subject received 2 FDC tablets of telmisartan/amlodipine 40/5 mg with and without rosuvastatin 20 mg, once daily for 9 consecutive days. In both parts, there was a 13-day washout period between treatments. Pharmacokinetic samples were collected up to 72 hours after the last dose in subjects who received rosuvastatin only, and up to 144 hours after the last dose in subjects who received telmisartan/amlodipine with or without rosuvastatin. Adverse events (AEs) were assessed via interviews and physical examinations.

FINDINGS

Forty-eight subjects were enrolled, of whom 19 in part 1 and 22 in part 2 completed the study. In Part 1, the 90% CIs of the geometric mean ratios (GMRs) (coadministration of rosuvastatin and telmisartan/amlodipine to monotherapy with rosuvastatin) of the primary pharmacokinetic parameters (AUCτ and Cmax,ss) were: rosuvastatin, 1.1436 to 1.3059 and 1.8970 to 2.3514, respectively; and N-desmethyl rosuvastatin, 0.8441 to 1.0200 and 1.1971 to 1.5457. In part 2, the 90% CIs of the GMRs (coadministration to monotherapy with telmisartan/amlodipine) were: telmisartan, 1.1204 to 1.4228 and 0.9940 to 1.5940; amlodipine, 0.9705 to 1.0636 and 0.9813 to 1.0779. There were no significant differences in the prevalences of AEs between the treatments, and all reported AEs were mild or moderate.

IMPLICATIONS

These results demonstrate that when rosuvastatin, telmisartan, and amlodipine are coadministered to healthy male subjects, pharmacokinetic exposure increases with respect to rosuvastatin and telmisartan, whereas no change occurs with respect to amlodipine. However, based on previous analyses, the degree of increase in the exposure observed was not regarded as clinically significant. All treatments were well-tolerated.

Authors+Show Affiliations

Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.Jeil Pharmaceutical Co, Ltd, Seoul, Republic of Korea.Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: kspark@yuhs.ac.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

27422590

Citation

Son, Mijeong, et al. "Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: a Randomized, Open-label, Multiple-dose, 2-period Crossover Study." Clinical Therapeutics, vol. 38, no. 8, 2016, pp. 1845-57.
Son M, Guk J, Kim Y, et al. Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study. Clin Ther. 2016;38(8):1845-57.
Son, M., Guk, J., Kim, Y., Woo Chae, D., Heo, Y. A., Soh, D., & Park, K. (2016). Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study. Clinical Therapeutics, 38(8), 1845-57. https://doi.org/10.1016/j.clinthera.2016.06.011
Son M, et al. Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: a Randomized, Open-label, Multiple-dose, 2-period Crossover Study. Clin Ther. 2016;38(8):1845-57. PubMed PMID: 27422590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study. AU - Son,Mijeong, AU - Guk,Jinju, AU - Kim,Yukyung, AU - Woo Chae,Dong, AU - Heo,Young-A, AU - Soh,Dongjun, AU - Park,Kyungsoo, Y1 - 2016/07/12/ PY - 2016/04/02/received PY - 2016/06/03/revised PY - 2016/06/10/accepted PY - 2016/7/17/entrez PY - 2016/7/17/pubmed PY - 2017/9/25/medline KW - amlodipine KW - drug–drug interaction KW - pharmacokinetic properties KW - rosuvastatin KW - telmisartan SP - 1845 EP - 57 JF - Clinical therapeutics JO - Clin Ther VL - 38 IS - 8 N2 - PURPOSE: Rosuvastatin, a hydroxy methylglutaryl coenzyme A reductase inhibitor; telmisartan, an angiotensin receptor blocker; and amlodipine, a calcium channel inhibitor, are commonly prescribed together for the treatment of hypertension nonresponsive to monotherapy and accompanied by dyslipidemia. However, the pharmacokinetic interactions among these 3 substances are not well understood. The aim of this study was to investigate the pharmacokinetic drug-drug interactions among rosuvastatin, telmisartan, and amlodipine in a healthy Korean male population. METHODS: In both parts of this randomized, open-label, multiple-dose, 2-part, 2-period crossover study, subjects aged 19 to 55 years were enrolled. In part 1, each subject received rosuvastatin 20 mg with and without 2 fixed-dose combination (FDC) tablets of telmisartan/amlodipine 40/5 mg, once daily for 9 consecutive days. In part 2, each subject received 2 FDC tablets of telmisartan/amlodipine 40/5 mg with and without rosuvastatin 20 mg, once daily for 9 consecutive days. In both parts, there was a 13-day washout period between treatments. Pharmacokinetic samples were collected up to 72 hours after the last dose in subjects who received rosuvastatin only, and up to 144 hours after the last dose in subjects who received telmisartan/amlodipine with or without rosuvastatin. Adverse events (AEs) were assessed via interviews and physical examinations. FINDINGS: Forty-eight subjects were enrolled, of whom 19 in part 1 and 22 in part 2 completed the study. In Part 1, the 90% CIs of the geometric mean ratios (GMRs) (coadministration of rosuvastatin and telmisartan/amlodipine to monotherapy with rosuvastatin) of the primary pharmacokinetic parameters (AUCτ and Cmax,ss) were: rosuvastatin, 1.1436 to 1.3059 and 1.8970 to 2.3514, respectively; and N-desmethyl rosuvastatin, 0.8441 to 1.0200 and 1.1971 to 1.5457. In part 2, the 90% CIs of the GMRs (coadministration to monotherapy with telmisartan/amlodipine) were: telmisartan, 1.1204 to 1.4228 and 0.9940 to 1.5940; amlodipine, 0.9705 to 1.0636 and 0.9813 to 1.0779. There were no significant differences in the prevalences of AEs between the treatments, and all reported AEs were mild or moderate. IMPLICATIONS: These results demonstrate that when rosuvastatin, telmisartan, and amlodipine are coadministered to healthy male subjects, pharmacokinetic exposure increases with respect to rosuvastatin and telmisartan, whereas no change occurs with respect to amlodipine. However, based on previous analyses, the degree of increase in the exposure observed was not regarded as clinically significant. All treatments were well-tolerated. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/27422590/Pharmacokinetic_Interaction_Between_Rosuvastatin_Telmisartan_and_Amlodipine_in_Healthy_Male_Korean_Subjects:_A_Randomized_Open_label_Multiple_dose_2_period_Crossover_Study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(16)30402-7 DB - PRIME DP - Unbound Medicine ER -