Tags

Type your tag names separated by a space and hit enter

Pharmacokinetic interaction between rosuvastatin and olmesartan: a randomized, open-label, 3-period, multiple-dose crossover study in healthy Korean male subjects.
Clin Ther. 2014 Aug 01; 36(8):1159-70.CT

Abstract

PURPOSE

Rosuvastatin has been widely used in combination with olmesartan for the treatment of dyslipidemia accompanied by hypertension. With no information currently available on the interaction between the 2 drugs, a pharmacokinetic study was conducted to investigate the influence of rosuvastatin on olmesartan and vice versa when the 2 drugs were coadministered. The purpose of this study was to investigate the pharmacokinetic profile of coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet and the associated drug-drug interaction in healthy Korean male volunteers.

METHODS

This was a randomized, open-label, 3-period, multiple-dose crossover study. Eligible subjects were aged 20 to 50 years and within 20% of their ideal body weight. After being randomly assigned to 6 groups of equal number, subjects received each of the following 3 formulations once a day for 7 consecutive days with an 8-day washout period between the formulations: rosuvastatin 20-mg tablet, olmesartan 40-mg tablet, and coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determined for rosuvastatin, its active metabolite (N-desmethyl rosuvastatin), and olmesartan. Adverse events were evaluated based on subject interviews and physical examinations.

FINDINGS

Among the 36 enrolled subjects, 34 completed the study (mean [range] age, 28.6 [23-49] y; mean [range] weight, 66.4 [52.2-78.7] kg). The 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters for the coadministration of the 2 drugs to the mono-administration of each drug were 85.14% to 96.08% for AUCτ and 81.41% to 97.48% for Css,max for rosuvastatin, and 77.55% to 89.48% for AUCτ and 75.62% to 90.12% for Css,max for N-desmethyl rosuvastatin; those values were 95.61% to 102.57% for AUCτ and 91.73% to 102.98% for Css,max for olmesartan. Dizziness was the most frequently noted adverse drug reaction, occurring in 1 subject receiving mono-administration of rosuvastatin, 1 subject receiving mono-administration of olmesartan, and 4 subjects receiving coadministration of rosuvastatin and olmesartan. All the adverse events were expected, and there was no significant difference in the incidence between the 2 formulations.

IMPLICATIONS

This study suggests that rosuvastatin and olmesartan did not significantly influence each other's pharmacokinetics when coadministered. Although the pharmacokinetics of N-desmethyl rosuvastatin were influenced by olmesartan, such interactions were considered clinically insignificant. All 3 formulations were well tolerated, and no serious adverse events or drug reactions were noted.

Authors+Show Affiliations

Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.DDS Research Laboratory, Daewoong Pharmaceutical Co, Ltd, Gyeonggi-Do, South Korea.Medical Department, Daewoong Pharmaceutical Co, Ltd, Seoul, South Korea.Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea. Electronic address: kspark@yuhs.ac.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25017182

Citation

Roh, Hyerang, et al. "Pharmacokinetic Interaction Between Rosuvastatin and Olmesartan: a Randomized, Open-label, 3-period, Multiple-dose Crossover Study in Healthy Korean Male Subjects." Clinical Therapeutics, vol. 36, no. 8, 2014, pp. 1159-70.
Roh H, Son H, Lee D, et al. Pharmacokinetic interaction between rosuvastatin and olmesartan: a randomized, open-label, 3-period, multiple-dose crossover study in healthy Korean male subjects. Clin Ther. 2014;36(8):1159-70.
Roh, H., Son, H., Lee, D., Chang, H., Yun, C., & Park, K. (2014). Pharmacokinetic interaction between rosuvastatin and olmesartan: a randomized, open-label, 3-period, multiple-dose crossover study in healthy Korean male subjects. Clinical Therapeutics, 36(8), 1159-70. https://doi.org/10.1016/j.clinthera.2014.06.022
Roh H, et al. Pharmacokinetic Interaction Between Rosuvastatin and Olmesartan: a Randomized, Open-label, 3-period, Multiple-dose Crossover Study in Healthy Korean Male Subjects. Clin Ther. 2014 Aug 1;36(8):1159-70. PubMed PMID: 25017182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic interaction between rosuvastatin and olmesartan: a randomized, open-label, 3-period, multiple-dose crossover study in healthy Korean male subjects. AU - Roh,Hyerang, AU - Son,Hankil, AU - Lee,Donghwan, AU - Chang,HeeChul, AU - Yun,Chohee, AU - Park,Kyungsoo, Y1 - 2014/07/10/ PY - 2014/03/31/received PY - 2014/06/18/revised PY - 2014/06/19/accepted PY - 2014/7/15/entrez PY - 2014/7/16/pubmed PY - 2016/3/22/medline KW - drug–drug interaction KW - olmesartan KW - pharmacokinetics KW - rosuvastatin SP - 1159 EP - 70 JF - Clinical therapeutics JO - Clin Ther VL - 36 IS - 8 N2 - PURPOSE: Rosuvastatin has been widely used in combination with olmesartan for the treatment of dyslipidemia accompanied by hypertension. With no information currently available on the interaction between the 2 drugs, a pharmacokinetic study was conducted to investigate the influence of rosuvastatin on olmesartan and vice versa when the 2 drugs were coadministered. The purpose of this study was to investigate the pharmacokinetic profile of coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet and the associated drug-drug interaction in healthy Korean male volunteers. METHODS: This was a randomized, open-label, 3-period, multiple-dose crossover study. Eligible subjects were aged 20 to 50 years and within 20% of their ideal body weight. After being randomly assigned to 6 groups of equal number, subjects received each of the following 3 formulations once a day for 7 consecutive days with an 8-day washout period between the formulations: rosuvastatin 20-mg tablet, olmesartan 40-mg tablet, and coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determined for rosuvastatin, its active metabolite (N-desmethyl rosuvastatin), and olmesartan. Adverse events were evaluated based on subject interviews and physical examinations. FINDINGS: Among the 36 enrolled subjects, 34 completed the study (mean [range] age, 28.6 [23-49] y; mean [range] weight, 66.4 [52.2-78.7] kg). The 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters for the coadministration of the 2 drugs to the mono-administration of each drug were 85.14% to 96.08% for AUCτ and 81.41% to 97.48% for Css,max for rosuvastatin, and 77.55% to 89.48% for AUCτ and 75.62% to 90.12% for Css,max for N-desmethyl rosuvastatin; those values were 95.61% to 102.57% for AUCτ and 91.73% to 102.98% for Css,max for olmesartan. Dizziness was the most frequently noted adverse drug reaction, occurring in 1 subject receiving mono-administration of rosuvastatin, 1 subject receiving mono-administration of olmesartan, and 4 subjects receiving coadministration of rosuvastatin and olmesartan. All the adverse events were expected, and there was no significant difference in the incidence between the 2 formulations. IMPLICATIONS: This study suggests that rosuvastatin and olmesartan did not significantly influence each other's pharmacokinetics when coadministered. Although the pharmacokinetics of N-desmethyl rosuvastatin were influenced by olmesartan, such interactions were considered clinically insignificant. All 3 formulations were well tolerated, and no serious adverse events or drug reactions were noted. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/25017182/Pharmacokinetic_interaction_between_rosuvastatin_and_olmesartan:_a_randomized_open_label_3_period_multiple_dose_crossover_study_in_healthy_Korean_male_subjects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(14)00386-5 DB - PRIME DP - Unbound Medicine ER -