Track topics on Twitter Track topics that are important to you
This phase 1 study (CO-338-044; NCT02740712), conducted in patients with an advanced solid tumor, evaluated the effect of the poly(ADP-ribose) polymerase inhibitor rucaparib on the pharmacokinetics of caffeine 200 mg, warfarin 10 mg, omeprazole 40 mg, and midazolam 2 mg (cytochrome P450 [CYP] 1A2, CYP2C9, CYP2C19, and CYP3A substrates; dosed as a cocktail) and digoxin 0.25 mg (P-glycoprotein substrate; dosed separately) without rucaparib and following oral rucaparib 600 mg twice daily (BID). Geometric mean (GM) ratios (90% CI) of AUC from time zero to last quantifiable measurement with and without rucaparib were: caffeine, 2.26 (1.93-2.65); S-warfarin, 1.49 (1.40-1.58); omeprazole, 1.55 (1.32-1.83); midazolam, 1.39 (1.14-1.68); and digoxin, 1.20 (1.12-1.29). There was limited effect on peak concentration of the substrates (GM ratios, 0.99-1.13). At steady state, rucaparib 600 mg BID moderately inhibited CYP1A2, weakly inhibited CYP2C9, CYP2C19, and CYP3A, and marginally increased digoxin exposure. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Clinical and translational science
ASP8477 (molecular weight 325.36 g/mol) is a fatty acid amide hydrolase inhibitor intended for the treatment of neuropathic pain. Results from in vitro studies indicated that ASP8477 is a direct inhib...
Genetic polymorphism is one of the most important factors responsible for interindividual and interethnic variability in drug response. Studies in major populations, ie, Caucasians, Asians, and Africa...
Hypericum perforatum L. (St. John's wort) is used to treat mild-to-moderate depression. Its potential safety risks are pharmacokinetic drug interactions via cytochrome P450 enzymes and P-glycoprotein,...
Cytochromes P450 (P450s) and their genetic variants in humans are important drug-metabolizing enzymes partly accounted for inter-individual variations in drug metabolism and toxicity. However, these g...
The research evaluated point-of-care drug interaction resources for scope, completeness, and consistency in drug-ethanol and drug-tobacco content.
This study will investigate the drug-drug interactions (DDIs) between rucaparib and oral rosuvastatin (Arm A), and between rucaparib and oral ethinylestradiol and levonorgestrel (Arm B), w...
A Study to Evaluate the Effect of Oral Doses of JNJ-54175446 on the Inhibition of Cytochrome P450 CYP3A4, CYP2C9, CYP1A2 and CYP2D6 Activity and the Induction of CYP2B6 and CYP2C19 Activity Using a Multiple Probe Substrate Cocktail in Healthy Subjects
The main purpose of this study is to determine the potential inhibitory/inducing effects of JNJ-54175446 after single and repeated dosing on the single-dose pharmacokinetics (PK) of a cock...
The purpose of this study is to assess pharmacokinetic concentrations of multiple probes alone followed by assessment of the same drug pharmacokinetic concentrations when the patient has s...
The purpose of this study to evaluate the effect of concomitant administration of GBT440 on caffeine (a CYP1A2 probe substrate), S warfarin (a CYP2C9 probe substrate), omeprazole (a CYP2C1...
The purpose of this study is to determine whether AZD1775 has any effect on the pharmacokinetics (PK) of three compounds (caffeine, omeprazole, and midazolam) that are probes for common dr...
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.
A cytochrome P-450 monooxygenase that can be induced by polycyclic aromatic xenobiotics in the liver of human and several animal species. This enzyme is of significant clinical interest due to the large number of drug interactions associated with its induction and its metabolism of THEOPHYLLINE. Caffeine is considered to be a model substrate for this enzyme. CYP1A2 activity can also be increased by environmental factors such as cigarette smoking, charbroiled meat, cruciferous vegetables, and a number of drugs including phenytoin, phenobarbital, and omeprazole.
Specific effects of drugs and substances on metabolic pathways such as those occurring through the CYTOCHROME P-450 ENZYME SYSTEM. These include effects that often result in DRUG INTERACTIONS; FOOD-DRUG INTERACTIONS; and HERB-DRUG INTERACTIONS.
Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
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...
Polymerase Chain Reaction (PCR)
PCR (Polymerase Chain Reaction) uses the ability of DNA polymerase (enzymes that create DNA molecules by assembling nucleotides, the building blocks of DNA. These enzymes are essential to DNA replication and usually work in pairs to create two ident...