Evaluation of Pharmacokinetic Drug Interactions of the Direct-Acting Antiviral Agents Elbasvir and Grazoprevir with Pitavastatin, Rosuvastatin, Pravastatin, and Atorvastatin in Healthy Adults
| Autor: | Christine Fandozzi, Deborah Panebianco, Luzelena Caro, Dennis Wolford, Zifang Guo, Iain P. Fraser, Dennis Swearingen, Vanessa Levine, Hwa-Ping Feng, Thomayant Prueksaritanont, Joan R. Butterton, Marian Iwamoto, Wendy W. Yeh |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Elbasvir
Statin business.industry medicine.drug_class Atorvastatin nutritional and metabolic diseases General Medicine 030204 cardiovascular system & hematology Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Grazoprevir Pharmacokinetics medicine lipids (amino acids peptides and proteins) Pharmacology (medical) Rosuvastatin cardiovascular diseases Pitavastatin business Pravastatin medicine.drug |
| Zdroj: | Clinical Drug Investigation. 41:133-147 |
| ISSN: | 1179-1918 1173-2563 |
| Popis: | Many people infected with hepatitis C virus have comorbidities, including hypercholesterolemia, that are treated with statins. In this study, we evaluated the drug–drug interaction potential of the hepatitis C virus inhibitors elbasvir (EBR) and grazoprevir (GZR) with statins. Pitavastatin, rosuvastatin, pravastatin, and atorvastatin are substrates of organic anion-transporting polypeptide 1B, whereas rosuvastatin and atorvastatin are also breast cancer resistance protein substrates. Three open-label, phase I clinical trials in healthy adults were conducted with multiple daily doses of oral GZR or EBR/GZR and single oral doses of statins. Trial 1: GZR 200 mg plus pitavastatin 10 mg. Trial 2: Part 1, GZR 200 mg plus rosuvastatin 10 mg, then EBR 50 mg/GZR 200 mg plus rosuvastatin 10 mg; Part 2, EBR 50 mg/GZR 200 mg plus pravastatin 40 mg. Trial 3: EBR 50 mg/GZR 200 mg plus atorvastatin 10 mg. Neither GZR nor EBR pharmacokinetics were meaningfully affected by statins. Coadministration of EBR/GZR did not result in clinically relevant changes in the exposure of pitavastatin or pravastatin. However, EBR/GZR increased exposure to rosuvastatin (126%) and atorvastatin (94%). Coadministration of statins plus GZR or EBR/GZR was generally well tolerated. Although statins do not appreciably affect EBR or GZR pharmacokinetics, EBR/GZR can impact the pharmacokinetics of certain statins, likely via inhibition of breast cancer resistance protein but not organic anion-transporting polypeptide 1B. Coadministration of EBR/GZR with pitavastatin or pravastatin does not require adjustment of either dose of statin, whereas the dose of rosuvastatin and atorvastatin should be decreased when coadministered with EBR/GZR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink