PharmPK Discussion - PK impact of renal or hepatic impairment

• On 12 Aug 2013 at 11:20:51, F.Frerart sent the message
  

  
  Dear all,
  
  We would like to conduct clinical trials to assess the impact of renal or hepatic impairment on the
  pharmacokinetics of a new drug.
  In population of normal healthy volunteers, after a single dose, we normally collect PK plasma
  samples until 24 hours post-dose.
  In renal or hepatic-impaired subjects, we expect the need of additional PK samples after 24 hours to
  properly assess the PK paramters, however we are not sure until how many hours post-dose we should
  keep collecting samples.
  May somebody be of any help on this subject?
  Many thanks in advance.
  F.Frerart
  
  

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• On 12 Aug 2013 at 13:06:34, Ahmed Nader sent the message
  

  
  Hello,
  
  If you know the fraction metabolized (fm) and fraction excreted (fe) of your drug in healthy
  individuals, you can predict the drop in total clearance in different degrees of renal or hepatic
  impairment and hence can predict the increase in half life. Your PK samples should cover at least
  3-4 half lives.
  
  Hope this helps.
  
  Regards
  
  Ahmed Nader, PhD
  Qatar University College of Pharmacy
  
  

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• On 12 Aug 2013 at 16:17:07, Toufigh Gordi sent the message
  

  
  Hi,
  
  To start with, I think you should look back at the available data from
  studies that already have been done. If you have informative PK data in
  plasma and the urinary excreted amounts in subjects, you can develop a
  PK model and find out more about the contribution of the urinary
  elimination to the total clearance of the drug. Once the model is
  developed, you can simulate different variations of kidney functions and
  decide what to do in your next study, e.g., if there is need for a dose
  reduction or what sampling duration you should consider.
  
  You can take a look at: Regadenoson pharmacokinetics and tolerability in
  subjects with impaired renal function. Gordi T, Blackburn B, Lieu H. J
  Clin Pharmacol. 2007 Jul;47(7):825-33.
  
  

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• On 12 Aug 2013 at 16:18:09, Masoud Jamei sent the message
  

  
  Hi
  
  This is a case where modelling and simulation can be a big help to design your clinical study
  appropriately. As a follow up to what Ahmed just said if you know fm and fe values (or alternatively
  physiochemical and metabolism kinetic of your drug) and also know what physiological and biological
  changes happen in patients with renal or hepatic impairment then you can predict PK changes, please
  see the following papers:
  
  http://www.ncbi.nlm.nih.gov/pubmed/?term=22115405
  http://www.ingentaconnect.com/content/adis/cpk/2010/00000049/00000003/art00003
  http://dx.doi.org/10.1002/bdd.1771
  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171651/
  
  Regards
  Masoud
  Toufigh
  
  

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