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.

Swallowing Tablets and Capsules Increases the Risk of Penetration and Aspiration in Patients with Stroke-Induced Dysphagia

“…Furthermore, all of these drugs could have been either suspended instead of being crushed or replaced by pharmaceutically or therapeutically equivalent dosage forms for which crushing or suspending is permitted. This finding highlights the importance of adequate information sources for the nursing staff and physicians [38]. A significant proportion of stroke patients has difficulties swallowing solid dosage forms; however, the patients' self-evaluation and commonly performed assessment tests did not reliably identify those patients.…”

“…In this context, potential drug-food interactions/incompatibilities, which can affect the pharmacokinetics of the active ingredient, have to be considered [38,39] (e.g., dairy products can influence the absorption of ciprofloxacin [40] or enteric coatings can be damaged by food with a pH similar to that in the small intestine [39]). To avoid such incompatibilities, it should be considered to ingest drugs with, e.g., TMW, products that have been specifically developed for patients with dysphagia and can be used with medicines without any concern.…”

Clinical implications of food–drug interactions with small-molecule kinase inhibitors

“…Other foods and beverages can have an effect on SMKI bioavailability (table 5). 2,9,27,63,64,[71][72][73][74] Concomitant grapefruit juice intake was studied for ibrutinib (115% AUC increase), 27 imatinib (2% increase in minimal plasma concentration [C min ]), 71 and nilotinib (29% AUC increase). 73 However, since the three study designs are very different, it is difficult to extrapolate their results to other CYP3A4metabolised SMKIs.…”

Influence of Cow’s Milk and Esomeprazole on the Absorption of Erlotinib: A Randomized, Crossover Pharmacokinetic Study in Lung Cancer Patients

“…In line with milk, yoghurt (0.4% fat [24]) is not expected to interact with erlotinib absorption and could also be considered safe. Coadministration with yoghurt was previously studied and was considered safe for the TKI nilotinib [3,25].…”