PharmPK Discussion - Acyclovir in Obese Patients

• On 20 Sep 2011 at 08:54:17, "Bikin, Dale" (Dale.Bikin.-at-.bannerhealth.com) sent the message
  

  
  Dear Colleagues
  
  We are coming into the season where we are increasingly using IV acyclovir. The question
  afoot is how best to dose it in obese patients.
  
  Text books suggest dosing based on ideal body weight. The sole research I could find is
  embodied in an ICAAC abstract from 1991 (#765).
  The study used 5 normal weight (96.3+/-15.4% IBW) and 7 morbidly obese (203+/-20.6% IBW)
  weight healthy females. They used noncompartmental analysis, collecting levels for up to
  12 hours after the end of the infusion (5mg/kg x 1, mean doses 288+/-33mg & 532+/-75 mg). So
  patient weights were about 58 kg and 106 kg. Reported VDss were 42.5 +/- 8.7 L vs 43.5 +/- 5.7
  L and 0.74 +/- 0.12 L/kg vs 0.42 +/- 0.1 L/kg total body weight. Thus the recommendation for
  dosing based on ideal body weight.
  
  Acyclovir is said to distribute into essentially the body water, so a 0.6 L/kg would be
  reasonable.  The Acyclovir Symposium from the American Journal of Medicine provides a
  table of PK parameters from adult studies. The average VDss values range from 41.4 L to 55
  L. When normalized to 1.73M^2, the values were 25 to 45% higher. This suggests to me we
  are again talking about patients in the 50-60 kg range.
  
  The acute care population we serve can easily be admitted with body weight 3-4 x IBW. So
  the question is whether the body water associated with the excess body weight is
  significant enough to justify/necessitate a "higher" dose than a 10mg/kg IBW dose
  (certainly adjusted for renal function) or not. Leonid Berezhkovskiy provides a nice
  treatise on estimating steady state distribution volume for obese patients from normal
  subjects (JPharmSci  2011;100:2482). It would seem that there IS a point at which we
  really do need to make a dose adjustment, but I am not sure where that point might be.
  
  The big point is that we have specifically studied only 7 obese, female, normal healthy
  subjects that do not reflect the common obese population we serve. I would love to have
  some help clarifying my thoughts on this issue.
  
  Thanks
  
  Dale Bikin, Pharm D
  Banner Good Samaritan Pharmacy
  1111 E McDowell, Phoenix, AZ  85006
  

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• On 21 Sep 2011 at 16:47:20, "Fox, Shelley Chambers" (chams.-at-.wsu.edu) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dale, one approach might be to use a better estimate of LBW than IBW. Here are a couple of
  papers that discuss this:
  1. Green and Duffull. What is the best size descriptor to use for pharmacokinetic studies
  in the obese? Br J Clin Pharmacol, 58:2: 119-133 (2004)
  2. Janmahasatian S, et al. Lean Body Mass normalizes the effect of obesity on renal
  function. Br J Clin Pharmacol, 65:6 964-965 (2008) DOI: 10.1111/J.1365-2125.2008.03112.x
  3. Janmahasatian S, et al. Quantification of Lean Bodyweight, Clin Pharmacokinet 44: 10:
  1051-1065 (2005)
  
  Shelley Chambers Fox, PhD, CGP
  Clinical Associate Professor
  Washington State University
  Department of Pharmaceutical Sciences
  

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• On 22 Sep 2011 at 15:30:38, "Bikin, Dale" (Dale.Bikin.-a-.bannerhealth.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Shelly,
  Thanks for the thoughts. Unfortunately, I had already walked down that path with a similar
  thought pattern. The available data does not really allow one to directly translate volume
  data into the LBW.
  
  I was thinking of approaching it from the perspective of potential fluid volume in that
  excess adipose tissue mass. The answer I come up with is that it may not matter too much.
  Somehow, I think we will have to look at this more specifically in the very obese sick
  population.
  
  Thanks
  Dale
  
  

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Copyright 1995-2011 David W. A. Bourne (david@boomer.org)