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| http://dx.doi.org/10.1111/j.1365-2125.2012.04408.x | DOI Listing |
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Evaluation of the drug-drug interaction potential of brigatinib using a physiologically-based pharmacokinetic modeling approach.
CPT Pharmacometrics Syst Pharmacol
April 2024
Clinical Pharmacology, Takeda Development Center Americas, Inc., Lexington, Massachusetts, USA.
Brigatinib is an oral anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive metastatic non-small cell lung cancer. In vitro studies indicated that brigatinib is primarily metabolized by CYP2C8 and CYP3A4 and inhibits P-gp, BCRP, OCT1, MATE1, and MATE2K. Clinical drug-drug interaction (DDI) studies with the strong CYP3A inhibitor itraconazole or the strong CYP3A inducer rifampin demonstrated that CYP3A-mediated metabolism was the primary contributor to overall brigatinib clearance in humans.
View Article and Find Full Text PDFMechanisms and Clinical Significance of Pharmacokinetic Drug Interactions Mediated by FDA and EMA-approved Hepatitis C Direct-Acting Antiviral Agents.
Clin Pharmacokinet
October 2023
School of Pharmacy, Faculty of Medicine and Health, University of Sydney, New South Wales, 2006, Australia.
The treatment of patients infected with the hepatitis C virus (HCV) has been revolutionised by the development of direct-acting antiviral agents (DAAs) that target specific HCV proteins involved in viral replication. The first DAAs were associated with clinical problems such as adverse drug reactions and pharmacokinetic drug-drug interactions (DDIs). Current FDA/EMA-approved treatments are combinations of DAAs that simultaneously target the HCV N5A-protein, the HCV N5B-polymerase and the HCV NS3/4A-protease.
View Article and Find Full Text PDFNITROSOGENESIS OF SKIN CANCER: THE NITROSAMINE CONTAMINATION IN THE CALCIUM CHANNEL BLOCKERS (AMLODIPINE), BETA BLOCKERS (BISOPROLOL), SARTANS (VALSARTAN/LOSARTAN), ACE INHIBITORS (PERINDOPRIL/ENALAPRIL), TRICYCLIC ANTIDEPRESSANTS (MELITRACEN), SSRIS (PAROXETINE), SNRIS (VENLAFAXINE) AND METFORMIN: THE MOST PROBABLE EXPLANATION FOR THE RISING SKIN CANCER INCIDENCE.
Georgian Med News
June 2023
Onkoderma - Clinic for Dermatology, Venereology and Dermatologic Surgery, Sofia, Bulgaria; Department of Dermatology and Venereology, Medical Institute of Ministry of Interior, Sofia, Bulgaria.
The Nitrosogenesis of skin cancer is a newly introduced concept in medical science, the significance of which is yet to be the subject of detailed analyses and discussions. Contamination of the most commonly used drugs for systemic treatment worldwide (such as Angiotensin receptor II blockers/ARBs, ACE inhibitors, Beta blockers, Thiazide diuretics, Metformin, Ranitidine, Nizatidine, tricyclic antidepressants, anticoagulants/dabigatran, Rifampicin, calcium channel blockers, SSRIs/ selective serotonin reuptake inhibitors, Varenicline) is already a fact and is more than worrying but also indicative. It is "this relationship" that has been repeatedly described in the medical literature (initially) as an association, and subsequently now increasingly as a causal relationship, a pathogenetic relationship.
View Article and Find Full Text PDFEvaluation of the Potential for Cytochrome P450 and Transporter-Mediated Drug-Drug Interactions for Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor (FXR) Agonist.
Clin Pharmacokinet
April 2023
Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA.
Background And Objective: Cilofexor is a selective farnesoid X receptor (FXR) agonist in development for the treatment of nonalcoholic steatohepatitis and primary sclerosing cholangitis. Our objective was to evaluate potential drug-drug interactions of cilofexor as a victim and as a perpetrator.
Methods: In this Phase 1 study, healthy adult participants (n = 18-24 per each of the 6 cohorts) were administered cilofexor in combination with either perpetrators or substrates of cytochrome P-450 (CYP) enzymes and drug transporters.
Quantification of CYP3A and Drug Transporters Activity in Healthy Young, Healthy Elderly and Chronic Kidney Disease Elderly Patients by a Microdose Cocktail Approach.
Front Pharmacol
September 2021
Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Chulalongkorn University, Bangkok, Thailand.
Ageing and chronic kidney disease (CKD) affect pharmacokinetic (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP) 3A and drug transporter activities were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail. Healthy young participants ( = 20), healthy elderly participants ( = 16) and elderly patients with CKD ( = 17) received, in study period 1, a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin.
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