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Effects of Yogurt and Applesauce on the Oral Bioavailability of Nilotinib in Healthy Volunteers
Author(s) -
Yin Ophelia Q. P.,
Rudoltz Marc,
Galetic Ivana,
Filian Jeiry,
Krishna Arun,
Zhou Wei,
Custodio Joseph,
Golor Georg,
Schran Horst
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010384116
Subject(s) - nilotinib , bioavailability , medicine , capsule , oral administration , pharmacology , pharmacokinetics , confidence interval , tyrosine kinase , botany , receptor , biology
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.