Fevipiprant has a low risk of influencing co-medication pharmacokinetics: Impact on simvastatin and rosuvastatin in different SLCO1B1 genotypes.

08:00 EDT 10th June 2019 | BioPortfolio

Summary of "Fevipiprant has a low risk of influencing co-medication pharmacokinetics: Impact on simvastatin and rosuvastatin in different SLCO1B1 genotypes."

Fevipiprant, a prostaglandin D receptor 2 antagonist, is in clinical development as a treatment for asthma. The goal of this study was to assess the potential of fevipiprant to cause drug-drug interactions (DDI) as a perpetrator, that is, by altering the pharmacokinetics (PK) of co-medications. In vitro drug interaction studies of clinically relevant drug metabolizing enzymes and transporters were conducted for fevipiprant and its acyl glucuronide (AG) metabolite. Comparison of K values with unbound systemic or portal vein steady-state plasma exposure of fevipiprant and its AG metabolite revealed the potential for inhibition of organic anion transporting polypeptide 1B1 (OATP1B1) transporters (R-value of 5.99), while other targets including cytochrome P450 enzymes were not, or only marginally, inhibited. Consequently, an open-label, two-part, two-period, single-sequence clinical study assessed the effect of fevipiprant 450 mg QD on the pharmacokinetics of simvastatin 20 mg and rosuvastatin 20 mg, two statins with different dependency in OATP1B1-mediated hepatic uptake, in healthy adult volunteers. The study also assessed the pharmacogenetics of the SLCO1B1 gene, which encodes OATP1B1. Clinically, fevipiprant 450 mg QD showed a low potential for interaction and increased the peak concentrations of simvastatin acid and rosuvastatin by 2.23- and 1.87-fold, respectively, with little or no impact on total exposure. Genotype analysis confirmed that SLCO1B1 genotype influences statin pharmacokinetics to a similar extent either with or without fevipiprant co-administration. In summary, fevipiprant at 450 mg QD has only minor liabilities as a perpetrator for DDI.


Journal Details

This article was published in the following journal.

Name: Pulmonary pharmacology & therapeutics
ISSN: 1522-9629
Pages: 101809


DeepDyve research library

PubMed Articles [21721 Associated PubMed Articles listed on BioPortfolio]

Role of esterase mediated hydrolysis of simvastatin in human and rat blood and its impact on pharmacokinetic profiles of simvastatin and its active metabolite in rat.

Simvastatin is known as a pro-drug, which could be hydrolyzed by esterases to its active form, simvastatin acid. Although pharmacokinetics of simvastatin and simvastatin acid have been widely studied,...

No Effect of Digoxin on Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study.

This study evaluated the utility of combination of digoxin (0.25 mg) and rosuvastatin (5 mg) as a new transporter (P-gp/BCRP/OATP1B1/OATP1B3) probe cocktail (Oita combination) for drug-drug interactio...

Longitudinal Impacts of Gastric Bypass Surgery on Pharmacodynamics and Pharmacokinetics of Statins.

Undergoing Roux-en-Y gastric bypass (RYGB) is expected to affect orally administered drug absorption. Statins are commonly prescribed to patients with obesity for the prevention of atherosclerotic car...

Bioanalytical method development and its application to pharmacokinetics studies on Simvastatin in the presence of Piperine and two of its synthetic derivatives.

Piperine has been widely used as a bioenhancer. Simvastatin belongs to a group of medicines known as statins. It acts by inhibiting HMG CoA reductase and acts primarily as a hypolipidemic agent. In th...

Effects of Food and Gender on Pharmacokinetics of Rosuvastatin in a Chinese Population Based on 4 Bioequivalence Studies.

The effects of food and gender on the pharmacokinetics of rosuvastatin in healthy Chinese subjects were investigated from 4 bioequivalence studies. These studies were designed as randomized, open-labe...

Clinical Trials [14617 Associated Clinical Trials listed on BioPortfolio]

Mercury II - Compare the Efficacy and Safety of Lipid Lowering Agents Atorvastatin and Simvastatin With Rosuvastatin in High Risk Subjects With Type IIa and IIb Hypercholesterolemia

The purpose of this study is to determine whether treatment with rosuvastatin following atorvastatin or simvastatin treatment will improve health outcomes for patients at high risk of Cor...

Drug Interaction Study of MGL-3196 With Rosuvastatin and Simvastatin

The purpose of this study is to determine whether MGL-3196 alters the pharmacokinetics of rosuvastatin and/or simvastatin in healthy male subjects and female subjects not of child-bearing ...

Evaluate the Efficacy and Safety of Rosuvastatin Versus Simvastatin in Type 2 Diabetic Patients With Dyslipidemia

This is a phase IV, randomized, open-label, parallel-arm, comparative and forced- titration study to compare the efficacy and safety of rosuvastatin versus simvastatin in patients with typ...

A Study to Investigate the Interaction of GSK1292263 With Rosuvastatin and Simvastatin in Healthy Subjects

This study is a Phase I, open-label, single-sequence drug interaction study to evaluate the effect of repeated doses of GSK1292263 on the pharmacokinetics of rosuvastatin and simvastatin i...

12-week Open-label, Phase IIIb Comparing Efficacy and Safety of Rosuvastatin (CRESTOR™) in Combination With Ezetimibe

The purpose of this study is to determine whether treatment of Rosuvastatin (CRESTOR™) or Simvastatin given as monotherapy or given in combination with Ezetimibe, will lower the Low De...

Medical and Biotech [MESH] Definitions

A pharmaceutical preparation of ezetimibe and simvastatin that is used in the treatment of HYPERCHOLESTEROLEMIA and HYPERLIPIDEMIAS.


Efforts to reduce risk, to address and reduce incidents and accidents that may negatively impact healthcare consumers.

Prospective risk assessment tool aimed at identifying potential risks and their impact in healthcare settings.

The formal process of obtaining a complete and accurate list of each patient's current home medications including name, dosage, frequency, and route of administration, and comparing admission, transfer, and/or discharge medication orders to that list. The reconciliation is done to avoid medication errors.

Quick Search


DeepDyve research library

Relevant Topics

Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Statins (or HMG-CoA reductase inhibitors) are a class of drug used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been as...

Searches Linking to this Article