Related Experiment Video
Updated: Apr 22, 2026
13:51
Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
Published on: November 11, 2018
9.4K
Pharmacokinetic interactions between simvastatin and setipiprant, a CRTH2 antagonist
Martine Gehin1, Patricia N Sidharta, Carmela Gnerre
1Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123, Allschwil, Switzerland, martine.gehin-beurne@actelion.com.
European Journal of Clinical Pharmacology
|October 18, 2014
Summary
Setipiprant, an investigational drug for allergies and asthma, showed minimal impact on simvastatin pharmacokinetics. This suggests setipiprant does not clinically affect CYP3A4 drug metabolism.
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Pharmacology
Background:
- Setipiprant is a selective CRTH2 antagonist explored for allergic rhinitis and asthma.
- In vitro studies indicated weak CYP3A4 induction potential for setipiprant.
- Potential for gut-level interactions with setipiprant at high doses (1,000 mg b.i.d.) could not be ruled out.
Purpose of the Study:
- To evaluate the pharmacokinetic interaction between setipiprant and simvastatin.
- To determine if setipiprant modulates CYP3A4 activity in vivo.
Main Methods:
- An open-label study involving 22 healthy males.
- Simvastatin (40 mg) was administered alone and concomitantly with setipiprant (1,000 mg b.i.d. for 9 days).
Main Results:
- Setipiprant administration resulted in a 9% decrease in simvastatin Cmax and a 16% decrease in AUC0-∞.
- Exposure to simvastatin acid was similar, with geometric mean ratios for AUC0-∞ within the 0.8-1.25 range.
- The median tmax of simvastatin acid occurred earlier when co-administered with setipiprant.
Conclusions:
- Setipiprant exhibits minimal impact on simvastatin pharmacokinetics.
- The drug does not appear to modulate CYP3A4 in a clinically significant manner.
Related Concept Videos
01:25Pharmacokinetics: Drug–Drug Interactions
792
Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
792
01:26Pharmacokinetics: Drug–Food and Drug–Viral Interactions
651
A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of...
651
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
912
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
912
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
375
Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
375
01:18Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism
377
Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...
377
01:30Drug toxicity: Drug–Drug Interaction
405
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
405