Effects of commonly administered agents and genetics on nebivolol pharmacokinetics: drug-drug interaction studies.
Drug interactions are a significant clinical concern, particularly in patients with conditions such as heart disease and hypertension, in whom coadministration of multiple drugs is common. Nebivolol is a selective β(1)-blocker with vasodilatory properties approved for the treatment of hypertension. Drug-drug interactions were investigated when nebivolol was coadministered to subjects classified as poor CYP2D6 metabolizers and extensive CYP2D6 metabolizers who were receiving other drugs commonly administered to patients with hypertension or compounds metabolized by cytochrome P450 (CYP) 2D6. There were no drug-drug interactions when nebivolol was coadministered with hydrochlorothiazide, furosemide, ramipril, losartan, digoxin, or warfarin. Coadministration with fluoxetine (also metabolized by CYP2D6) in extensive CYP2D6 metabolizers impeded the apparent clearance of nebivolol. The authors conclude that nebivolol is safe and well tolerated regardless of genotype and type of medication coadministered.
Lindamood
Charles
C
Toxicology and Clinical Pharmacology, Forest Research Institute, Harborside Financial Center; Plaza V, Jersey City, NJ 0731, USA. charles.lindamood@frx.com
Ortiz
Stephan
S
Shaw
Andrew
A
Rackley
Russ
R
Gorski
J Christopher
JC
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001578:Benzopyrans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004347:Drug Interactions; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000493:pharmacokinetics; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics; D005838:Genotype; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000493:pharmacokinetics; D019808:Losartan / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D017257:Ramipril / Q000008:administration & dosage / Q000493:pharmacokinetics; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics; D055815:Young Adult
D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D005473:Fluoxetine; D000068577:Nebivolol; D006852:Hydrochlorothiazide; D014859:Warfarin; D004077:Digoxin; D005665:Furosemide; D019389:Cytochrome P-450 CYP2D6; D019808:Losartan; D017257:Ramipril