PharmPK Discussion - Different Tmax at different doses

• On 4 Aug 2013 at 23:13:41, Amrita Saxen sent the message
  

  
  Hi,
  
  In a dose proportionality study of an antithrombotic lead candidate, i am getting Tmax values 10,
  3.33 and 9.58 hrs at 10, 20 and 40 mg doses.
  
  So there is no pattern. Can anyone explain why at mid dose of 20 mg, the Tmax is approx less than
  half.
  
  Thanks in advance.
  
  Amrita Saxena
  Research Scholar
  Pharmacokinetics and Metabolism Div.
  Central Drug Research Institute,
  Lucknow, India-226020
  
  

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• On 5 Aug 2013 at 11:43:24, Vijay Kumar Sripuram sent the message
  

  
  Dear Amrita,
  
  Did you check the possibility of swap between samples during analysis particularly around Tmax?
  
  Except this, no assumption can be made with the information you provided.
  
  Best
  Vijay Kumar Sripuram
  Dr Reddy's Institute of Life Sciences
  University of Hyderabad
  Hyderabad, India.
  
  

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• On 5 Aug 2013 at 11:44:18, Deepak Bhatt sent the message
  

  
  Hi,
  I would like to suggest repeat your study.
  Deepak
  
  

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• On 5 Aug 2013 at 12:00:28, Walt Woltosz sent the message
  

  
  Amrita,
  
  Can you provide more information?
  
  Is the plasma concentration-time curve relatively flat for many hours?
  
  How many subjects per dose (all healthy?)?
  
  What was the formulation for each dose?
  
  Best regards,
  
  Walt
  
  Walt Woltosz
  Chairman and CEO
  Simulations Plus, Inc. (NASDAQ: SLP)
  42505 10th Street West
  Lancaster, CA 93534
  www.simulations-plus.com
  
  

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• On 5 Aug 2013 at 12:15:38, Pradeep Sathe sent the message
  

  
  Hi Amita,
  
  Are these average Tmax values? How many subjects were studied? Is this pattern seen with each
  individual subject?
  
  Sincerely..............pradeep
  
  

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• On 5 Aug 2013 at 12:51:11, Ed O'Connor (efoconnor.-a-.gmail.com) sent the message
  

  
  If faster
  Saturating a degradative enzyme or inducing a transport
  
  If slower
  Perhaps a
  Saturating a transport or inducing a degradative enzyme
  
  

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• On 5 Aug 2013 at 14:09:48, Rao Chennamaneni sent the message
  

  
  Amrita,
  
  I see a pattern, you have Tmax around 10 hr for both 10 and 40 mg/kg doses. This means at 20 mg/kg
  dose you had some issue. The possible reasons could be one of the following:
  
  	* issue with the formulation (precipitation etc.)
  	* age, sex, fasting conditions for all animals used in the study
  	* collecting samples in properly labelled tubes
  	* change of sample tubes during bio-analysis (majority of times labelling issues)
  	* finally, identifying data outliers
  
  I recommend to go for a serial dilution method while preparing different dose solutions or
  suspensions.
  
  Best,
  Rao Chennamaneni
  iVeena LLC., Moran Eye Center,
  SLC, Utah, USA.
  
  

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