The Effects of Multiple Doses of Fenofibrate on the Pharmacokinetics of Pravastatin and Its 3α-Hydroxy Isomeric Metabolite
| Autor: | Linda E. Gustavson, H. Daniel Yannicelli, Ramanuj Achari, Hans-Ulrich Esslinger, Titus Chira, Sarah M. Schweitzer, Stephan Koehne-Voss |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Metabolic Clearance Rate medicine.drug_class Metabolite Fibrate Pharmacology chemistry.chemical_compound Fenofibrate Isomerism Pharmacokinetics polycyclic compounds Humans Medicine Gemfibrozil Drug Interactions Pharmacology (medical) Adverse effect Active metabolite Hypolipidemic Agents Pravastatin business.industry Anticholesteremic Agents nutritional and metabolic diseases Middle Aged chemistry Area Under Curve Female lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors business Half-Life medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 45:947-953 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/0091270005278085 |
| Popis: | Published data indicate that coadministration of multiple doses of the fibrate drug, gemfibrozil, led to a 202% increase in pravastatin systemic exposure (area under the plasma concentration-time curve, AUC). To evaluate the effects of another fibrate drug, fenofibrate, on the pharmacokinetics of pravastatin, 24 healthy subjects took pravastatin (40 mg once daily) on study days 1 to 15 and fenofibrate (160 mg once daily) on study days 6 to 15. Blood samples were collected for 24 hours after dosing on days 5, 6, and 15. Plasma concentrations of pravastatin and its active metabolite, 3alpha-hydroxy-iso-pravastatin, were measured, and pharmacokinetics was assessed. Safety assessments were based on adverse events, physical examinations, electrocardiogram results, vital signs, and clinical laboratory testing. Safety results were unremarkable. Coadministration of fenofibrate had modest effects on pravastatin and 3alpha-hydroxy-iso-pravastatin systemic exposures (AUC). Increases in pravastatin systemic exposures (19%-28%, on average) and 3alpha-hydroxy-iso-pravastatin systemic exposures (24%-39%, on average) were observed upon coadministration, but individual changes were variable. Pravastatin and 3alpha-hydroxy-iso-pravastatin systemic exposures were not statistically significantly different following the 1st and 10th doses of fenofibrate. |
| Databáze: | OpenAIRE |
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