Pharmacokinetic profile of novel reduced-dose Danziten(TM) (nilotinib tablets) versus Tasigna® (nilotinib capsules): In vivo bioequivalence and population pharmacokinetic analysis Journal Article
| Authors: | Mauro, M.; Radich, J.; Jain, P.; Sequeira, D.; Bellanti, F.; Douer, D. |
| Article Title: | Pharmacokinetic profile of novel reduced-dose Danziten(TM) (nilotinib tablets) versus Tasigna® (nilotinib capsules): In vivo bioequivalence and population pharmacokinetic analysis |
| Abstract: | Purpose: To evaluate single dose pharmacokinetics (PK) of novel reduced-dose film coated DanzitenTM (nilotinib tablets) using a population PK approach, establish bioequivalence vs. Tasigna® (nilotinib capsules) and investigate food effects on PK of both formulations. Methods: A population PK model evaluating nilotinib capsules (300 or 400 mg) or tablets (142 or 190 mg) was developed using data from 14 single dose studies and > 30,000 plasma samples from healthy men and women. Steady-state nilotinib concentration–time profiles following twice daily dosing with various treatment and food conditions were simulated using a randomly sampled dataset of 50 subjects. Results: PK was characterized by a 2-compartment model with linear elimination and zero-order absorption with lag time. Bioequivalence was met for all steady state exposure metrics for both doses under fasted conditions. A milligram strength for nilotinib tablets ~ 50% lower than that for capsules resulted in bioequivalent nilotinib exposures. Administration with a low-fat meal under modified fasting conditions increased the bioavailability (BA) of 142 mg and 190 mg nilotinib tablets by 26.0% and 29.3%, respectively, vs. fasting; values for 300 mg and 400 mg capsules were 56.8% and 60.7%. Administration with a high-fat meal under modified fasting conditions increased the BA of 142 and 190 mg nilotinib tablets by 48.6% and 52.2%, respectively; values for 300 and 400 mg capsules were 180.6% and 183.3%. Conclusion: Nilotinib tablets 142 and 190 mg provide bioequivalent exposures to 300 mg and 400 mg capsules under fasted conditions and substantially smaller effects of food on exposure. © The Author(s) 2025. |
| Keywords: | adult; controlled study; middle aged; young adult; area under the curve; dose response; drug safety; comparative study; drug megadose; caloric intake; low drug dose; biological model; models, biological; randomized controlled trial; drug dosage form comparison; in vivo study; dose-response relationship, drug; chronic myeloid leukemia; pyrimidines; food; blood sampling; single drug dose; interaction; food drug interaction; food-drug interactions; drug bioavailability; time to maximum plasma concentration; drug absorption; drug half life; nilotinib; pyrimidine derivative; crossover procedure; administration, oral; fasting; normal human; bioavailability; biological availability; oral drug administration; drug elimination; compartment model; pharmacokinetic parameters; adherence; tablet; lipid diet; tablets; cross-over studies; drug disposition; microcapsule; low fat diet; bioequivalence; therapeutic equivalency; drug coating; population model; predictive model; humans; human; male; female; article; capsules; concentration at steady-state; drug capsule; maximum concentration; minimum concentration; therapeutic equivalence |
| Journal Title: | Cancer Chemotherapy and Pharmacology |
| Volume: | 95 |
| ISSN: | 0344-5704 |
| Publisher: | Springer |
| Date Published: | 2025-05-11 |
| Start Page: | 56 |
| Language: | English |
| DOI: | 10.1007/s00280-025-04777-6 |
| PUBMED: | 40349288 |
| PROVIDER: | scopus |
| PMCID: | PMC12066371 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
