title: Effects of yogurt and applesauce on the oral bioavailability of nilotinib in healthy volunteers.
abstract: Nilotinib, a potent orally bioavailable BCR-ABL tyrosine kinase inhibitor, is currently available as a hard gelatin capsule that must be swallowed whole. For patients who may have difficulty swallowing the intact capsule, an alternative mode of administration is desirable. The authors compared the bioavailability of nilotinib from the following administrations in 48 healthy subjects: (1) 400 mg nilotinib given as two 200-mg nilotinib intact capsules; (2) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of nonfat plain yogurt; and (3) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of applesauce. Nilotinib absorption was modestly increased following the administration of nilotinib dispersed in yogurt. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 1.31 (1.22-1.41), 1.11 (1.05-1.16), and 1.08 (1.02-1.15), respectively. Administration of nilotinib dispersed in applesauce showed equivalent bioavailability compared with administration of nilotinib as intact capsules. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 0.95 (0.88-1.02), 0.99 (0.94-1.04), and 0.97 (0.90-1.03), respectively. Each treatment was well tolerated in the study subjects. The data support a feasible alternative method of nilotinib administration; each capsule's contents may be dispersed in 1 teaspoon of applesauce and taken immediately.
authors.affiliation: Novartis Pharmaceuticals Corporation, 180 Park Avenue, Florham Park, NJ 07932, USA. Ophelia.yin@novartis.com
authors.forename: Ophelia Q P
authors.initials: OQ
authors.lastname: Yin
authors.forename: Marc
authors.initials: M
authors.lastname: Rudoltz
authors.forename: Ivana
authors.initials: I
authors.lastname: Galetic
authors.forename: Jeiry
authors.initials: J
authors.lastname: Filian
authors.forename: Arun
authors.initials: A
authors.lastname: Krishna
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Joseph
authors.initials: J
authors.lastname: Custodio
authors.forename: Georg
authors.initials: G
authors.lastname: Golor
authors.forename: Horst
authors.initials: H
authors.lastname: Schran
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules / Q000008:administration & dosage; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003680:Deglutition Disorders; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D027845:Malus; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D015014:Yogurt
chemical_list: D002214:Capsules; D011743:Pyrimidines; C498826:nilotinib