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Clinical evaluation of P-glycoprotein inhibition by venetoclax: a drug interaction study with digoxin
- Source :
- Xenobiotica. 48:904-910
- Publication Year :
- 2017
- Publisher :
- Informa UK Limited, 2017.
-
Abstract
- 1. Venetoclax is a novel, small molecule B-cell lymphoma-2 (BCL-2) inhibitor that has demonstrated clinical efficacy in a variety of haematological malignancies. Since venetoclax is an inhibitor of P glycoprotein (P-gp) transporter, a study was conducted in healthy, female volunteers to evaluate the effect of venetoclax on the pharmacokinetics of digoxin, a P-gp probe substrate. 2. Volunteers received a single oral dose of digoxin (0.5 mg) with or without a single oral dose of venetoclax (100 mg). Serial blood samples were obtained for pharmacokinetic assessments of digoxin and venetoclax and serial urine samples were obtained for measurement of digoxin concentrations. Safety was assessed throughout the study. 3. Coadministration of digoxin and venetoclax increased digoxin maximum observed plasma concentration (Cmax) by 35% and area under the plasma-concentration time curve (AUC0-∞) by 9%. Digoxin half-life, renal clearance and the fraction excreted unchanged in urine remained relatively similar. The results of this study indicate that venetoclax can increase the concentrations of P-gp substrates. Narrow therapeutic index P-gp substrates should be administered six hours prior to venetoclax to minimise the potential interaction.
- Subjects :
- Adult
Digoxin
Health, Toxicology and Mutagenesis
Cmax
Antineoplastic Agents
Urine
Pharmacology
Toxicology
030226 pharmacology & pharmacy
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Therapeutic index
Pharmacokinetics
Humans
Medicine
Drug Interactions
ATP Binding Cassette Transporter, Subfamily B, Member 1
Sulfonamides
Cross-Over Studies
Venetoclax
business.industry
General Medicine
Middle Aged
Drug interaction
Bridged Bicyclo Compounds, Heterocyclic
Crossover study
chemistry
030220 oncology & carcinogenesis
Female
business
Half-Life
medicine.drug
Subjects
Details
- ISSN :
- 13665928 and 00498254
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Xenobiotica
- Accession number :
- edsair.doi.dedup.....292490be75092050a66eae12e8688823