Scholarlink

Purpose <p>To evaluate single&#xa0;dose pharmacokinetics (PK) of novel reduced-dose film coated Danziten<sup>™</sup> (nilotinib tablets) using a population PK approach, establish bioequivalence vs. Tasigna<sup>®</sup> (nilotinib capsules) and investigate food effects on PK of both formulations.</p> Methods <p>A population PK model evaluating nilotinib capsules (300 or 400&#xa0;mg) or tablets (142 or 190&#xa0;mg) was developed using data from 14 single&#xa0;dose studies and &gt; 30,000 plasma samples from healthy men and women. Steady-state nilotinib concentration–time profiles following twice&#xa0;daily dosing with various treatment and food conditions were simulated using a randomly sampled dataset of 50 subjects.</p> Results <p>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&#xa0;mg and 190&#xa0;mg nilotinib tablets by 26.0% and 29.3%, respectively, vs. fasting; values for 300&#xa0;mg and 400&#xa0;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&#xa0;mg nilotinib tablets by 48.6% and 52.2%, respectively; values for 300 and 400&#xa0;mg capsules were 180.6% and 183.3%.</p> Conclusion <p>Nilotinib tablets 142 and 190&#xa0;mg provide bioequivalent exposures to 300&#xa0;mg and 400&#xa0;mg capsules under fasted conditions and substantially smaller effects of food on exposure.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pharmacokinetic profile of novel reduced-dose Danziten™ (nilotinib tablets) versus Tasigna® (nilotinib capsules): in vivo bioequivalence and population pharmacokinetic analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月11日

查看全文
  • Michael Mauro,
  • Jerald Radich,
  • Paras Jain,
  • David Sequeira,
  • Francesco Bellanti,
  • Dan Douer

摘要

Purpose

To evaluate single dose pharmacokinetics (PK) of novel reduced-dose film coated Danziten™ (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.