Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers
Dyslipidemia is a major risk factor for development of atherosclerosis and cardiovascular disease (CVD). Effective lipid-lowering therapies has led to CVD risk reduction. This study evaluated the possible pharmacokinetic interactions between fenofibrate, a peroxisome proliferators-activated receptor...
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MDPI AG
2020-09-01
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| Online Access: | https://www.mdpi.com/1999-4923/12/9/869 |
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| author | Hae Won Lee Woo Youl Kang Wookjae Jung Mi-Ri Gwon Kyunghee Cho Dong Heon Yang Young-Ran Yoon Sook Jin Seong |
| author_facet | Hae Won Lee Woo Youl Kang Wookjae Jung Mi-Ri Gwon Kyunghee Cho Dong Heon Yang Young-Ran Yoon Sook Jin Seong |
| author_sort | Hae Won Lee |
| collection | DOAJ |
| description | Dyslipidemia is a major risk factor for development of atherosclerosis and cardiovascular disease (CVD). Effective lipid-lowering therapies has led to CVD risk reduction. This study evaluated the possible pharmacokinetic interactions between fenofibrate, a peroxisome proliferators-activated receptors α agonist, and pitavastatin, a 3-hydoxy-3-methylglutaryl-coenzyme A reductase inhibitor, in healthy Korean subjects. The study design was an open-label, randomized, multiple-dose, three-period, and six-sequence crossover study with a 10-day washout in 24 healthy volunteers. It had three treatments: 160 mg of micronized fenofibrate once daily for 5 days; 2 mg of pitavastatin once daily for 5 days; and 160 mg of micronized fenofibrate with 2 mg of pitavastatin for 5 days. Serial blood samples were collected at scheduled intervals for up to 48 h after the last dose in each period to determine the steady-state pharmacokinetics of both drugs. Plasma concentrations of fenofibric acid and pitavastatin were measured using a validated high-performance liquid chromatography with the tandem mass spectrometry method. A total of 24 subjects completed the study. Pitavastatin, when co-administered with micronized fenofibrate, had no effect on the C<sub>max,ss</sub> and AUC<sub>τ,ss</sub> of fenofibric acid. The C<sub>max,ss</sub> and AUC<sub>τ,ss</sub> of pitavastatin were increased by 36% and 12%, respectively, when co-administered with fenofibrate. Combined treatment with pitavastatin and micronized fenofibrate was generally well tolerated without serious adverse events. Our results demonstrated no clinically significant pharmacokinetic interactions between micronized fenofibrate and pitavastatin when 160 mg of micronized fenofibrate and 2 mg of pitavastatin are co-administered. The treatments were well tolerated during the study, with no serious adverse events. |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T16:22:36Z |
| publishDate | 2020-09-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-87c7b0d179114769b7e3c57bf4a273e12023-11-20T13:29:39ZengMDPI AGPharmaceutics1999-49232020-09-0112986910.3390/pharmaceutics12090869Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy VolunteersHae Won Lee0Woo Youl Kang1Wookjae Jung2Mi-Ri Gwon3Kyunghee Cho4Dong Heon Yang5Young-Ran Yoon6Sook Jin Seong7Department of Molecular Medicine, School of Medicine, Kyungpook National University and Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu 41566, KoreaDepartment of Molecular Medicine, School of Medicine, Kyungpook National University and Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu 41566, KoreaDepartment of Molecular Medicine, School of Medicine, Kyungpook National University and Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu 41566, KoreaDepartment of Molecular Medicine, School of Medicine, Kyungpook National University and Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu 41566, KoreaAnalytical Research Division, Biocore Co. Ltd., Seoul 08511, KoreaDivision of Cardiology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, KoreaDepartment of Molecular Medicine, School of Medicine, Kyungpook National University and Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu 41566, KoreaDepartment of Molecular Medicine, School of Medicine, Kyungpook National University and Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu 41566, KoreaDyslipidemia is a major risk factor for development of atherosclerosis and cardiovascular disease (CVD). Effective lipid-lowering therapies has led to CVD risk reduction. This study evaluated the possible pharmacokinetic interactions between fenofibrate, a peroxisome proliferators-activated receptors α agonist, and pitavastatin, a 3-hydoxy-3-methylglutaryl-coenzyme A reductase inhibitor, in healthy Korean subjects. The study design was an open-label, randomized, multiple-dose, three-period, and six-sequence crossover study with a 10-day washout in 24 healthy volunteers. It had three treatments: 160 mg of micronized fenofibrate once daily for 5 days; 2 mg of pitavastatin once daily for 5 days; and 160 mg of micronized fenofibrate with 2 mg of pitavastatin for 5 days. Serial blood samples were collected at scheduled intervals for up to 48 h after the last dose in each period to determine the steady-state pharmacokinetics of both drugs. Plasma concentrations of fenofibric acid and pitavastatin were measured using a validated high-performance liquid chromatography with the tandem mass spectrometry method. A total of 24 subjects completed the study. Pitavastatin, when co-administered with micronized fenofibrate, had no effect on the C<sub>max,ss</sub> and AUC<sub>τ,ss</sub> of fenofibric acid. The C<sub>max,ss</sub> and AUC<sub>τ,ss</sub> of pitavastatin were increased by 36% and 12%, respectively, when co-administered with fenofibrate. Combined treatment with pitavastatin and micronized fenofibrate was generally well tolerated without serious adverse events. Our results demonstrated no clinically significant pharmacokinetic interactions between micronized fenofibrate and pitavastatin when 160 mg of micronized fenofibrate and 2 mg of pitavastatin are co-administered. The treatments were well tolerated during the study, with no serious adverse events.https://www.mdpi.com/1999-4923/12/9/869micronized fenofibratepharmacokineticsdrug-drug interactionpitavastatinsafety |
| spellingShingle | Hae Won Lee Woo Youl Kang Wookjae Jung Mi-Ri Gwon Kyunghee Cho Dong Heon Yang Young-Ran Yoon Sook Jin Seong Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers Pharmaceutics micronized fenofibrate pharmacokinetics drug-drug interaction pitavastatin safety |
| title | Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers |
| title_full | Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers |
| title_fullStr | Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers |
| title_full_unstemmed | Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers |
| title_short | Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers |
| title_sort | evaluation of the pharmacokinetic drug drug interaction between micronized fenofibrate and pitavastatin in healthy volunteers |
| topic | micronized fenofibrate pharmacokinetics drug-drug interaction pitavastatin safety |
| url | https://www.mdpi.com/1999-4923/12/9/869 |
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