Loading presentation...

Present Remotely

Send the link below via email or IM


Present to your audience

Start remote presentation

  • Invited audience members will follow you as you navigate and present
  • People invited to a presentation do not need a Prezi account
  • This link expires 10 minutes after you close the presentation
  • A maximum of 30 users can follow your presentation
  • Learn more about this feature in our knowledge base article

Do you really want to delete this prezi?

Neither you, nor the coeditors you shared it with will be able to recover it again.



Best practices on how to use simple flash animations in combination with prezi Path and Frames - to achieve a strong narrative.

Neal Rakesh

on 3 December 2010

Comments (0)

Please log in to add your comment.

Report abuse

Transcript of Nilotinib

Methods: Clinical Pharmacokinetics of the BCR-ABL
Tyrosine Kinase Inhibitor Nilotinib C Tanaka, OQP Yin, V Sethuraman, T Smith, X Wang, K Grouss, H Kantarjian, F Giles, OG Ottmann, L Galitz and H Schran Chronic Myeloid Leukemia (CML) Cancer of white blood cells (WBC)
Chromosomal Translocation
Diagnosis Goal Levels of WBCs Problem Imatinib resistance in CML Patients Solution Nilotinib
Tyrosine kinase inhibitor
Greater potency and selectivity
Antiproliferative activity Objective Understand the PK of Nilotinib
Phase I Dose Escalation

Study of Food-Related Effects in Healthy Subjects Ideal Dosing Regimen Nilotinib Phase I Dose-Escalation Patients
Philadelphia positive Imatinib-resistant
9 Dosage Types
Once Daily: 50 - 1,200 mg
Twice Daily: 400 & 600 mg
2 Hrs after breakfast (& after dinner)
28 Days Phase I Dose-Escalation: High Fat Meal High-fat breakfast
~1000 calories
15% protein, 35% carbs, 50% fat
Twice Daily
400 mg (n = 7)
600 mg (n = 3)
Treatment *Before Morning Dose Study of Food-Related Effects in Healthy Subjects Healthy Patient
Medical Records & Lab Tests
Restricted Intake
Light Breakfast
~500 calories
10% protein, 60% carbs, 30% fat
Single 400 mg dose
Fast 10 Hrs before morning dose
Eat high-fat breakfast 30 Mins before morning dose
Eat light breakfast 30 Mins/2 Hrs before morning dose Sample Collection for PK Analysis Blood Sample
Collect, Stand, Centrifuge, Store
Phase I Dose-Escalation
1x-Daily (Days 1, 15, 28)
2x-Daily (Days 1, 8, 15)
Study of food-related effects in healthy subjects
3 study periods
Same for all regimens Nilotinib Analytical Method Liquid chromatography-Tandem mass spectrometry (LC-MS)
Sample preparation, extraction, dehydration, dissolution
Sample analyzed HPLC separation
Mass spectrometry detection PK Analysis Used WinNonlin software to calculate:
C , t , C
AUC - trapezoidal rule
Terminal elimination rate (k)
t = ln(2)/k
CL = dose/AUC
V = dose/(AUC *k)
WBC count of patients were normalized against their baseline levels and compared with AUC max max min 1/2 0- 8 0-24 Hrs Statistical Methods Means, Std Dev, Coeff of var.
Median values and ranges for t
Food-intake related effects

Absence of food intake effect Linear mixed-effects model

AUC , AUC , & C
90% confidence interval, range from .80-1.25 max 0-t 0- 8 max Inhibit Phosphorylation Dose Escalation t - 3 Hrs
Steady State

C , AUC constant

Day 15: 1x/Day
Day 8: 2x/Day > 400 mg 1x/Day
400 mg 2x/Day max max 400 mg 2x/Day: 81.6% reduction WBC count Results Discussion Dose Escalation As Nilotinib , WBCs
400 mg 2x/Day: [Plasma] > IC
Solubility limited absorption

Interpatient variability Best Dosage: 400 mg, 2x/Day Nilotinib metabolism
Serum-albumin Study of Food - Related Effects in Healthy Subjects C AUC max 0-t Study of Food - Related Effects in Healthy Subjects Food affects absorption
Light meal
High fat meal
Increased dissolution
Delayed gastric emptying IMPORTANT
Maintain Consistent
Diet Conclusion Best Dosage
400 mg, 2x/Day
Food Consumption
High fat meal before
Maintain steady diet
More effective WBC than Imatinib References http://www.epgonline.org/images/cml/2143-a.gif
http://multivu.prenwswire.com/mnr/novartis/30191/images/ 30191-hi-Tasigna_Package.jpg
http://www.us.tasigna.com:80/index.jsp?usertrack.filter_applied=true&NovaId=2935376852770548811 Thank You 50 0- 8
Full transcript