PharmPK Discussion - Computing Urinary Excretion Fractions (fe) from Cmax and Tmax in urine

• On 31 Jul 2013 at 13:25:41, Kevin J. Bisceglia sent the message
  

  
  Hello,
  
  I'm writing to ask if it is possible to compute cumulative urinary excretion fractions (i.e.,
  percent of administered dose excreted unchanged, or as metabolite A) for a drug and its metabolites
  knowing only the following information:
  
  - Total dose (mg)
  - Cmax in urine (ng/mL)
  - Tmax in urine (h)
  - Time from administration to last detection (h)
  
  The drug in question is cocaine, and the data comes from this paper:
  
  Smith, M. L., et al., Urinary Excretion of Ecgonine and Five Other Cocaine Metabolites Following
  Controlled Oral, Intravenous, Intranasal, and Smoked Administration of Cocaine J Anal Toxicol (2010)
  34 (2): 57-63 doi:10.1093/jat/34.2.57
  Link: http://jat.oxfordjournals.org/content/34/2/57.long
  
  I don't have urine volumes, concentration-time profiles, or (direct) information about excretion
  rates, so I'm not sure if it can be done.  However, I am a novice at PK modeling, so please forgive
  my ignorance.
  
  Thanks in advance for your help,
  
  Kevin
  
  --
  Kevin J. Bisceglia, Ph.D.
  Hofstra University
  Hempstead, NY 11549
  kevin.bisceglia.-a-.hofstra.edu
  
  

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• On 2 Aug 2013 at 13:25:56, Ed O'Connor (efoconnor.-a-.gmail.com) sent the message
  

  
  Estimating is conjecture.  Measure it
  --
  And you will not see cocaine but benzoylecgonine instead.   You may see ethyl or propylecgonine!!!
  --
  And there is always Clarkes isolation and identification of drugs.  Exc pk
  --
  
  Ed O'Connor 
  
  

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• On 2 Aug 2013 at 19:56:10, Peter W. Mullen (pmullen.at.kemic.com) sent the message
  

  
  Hi Ed & Kevin,
  
  For those with an interest in forensic pharmacokinetics, a model of the urinary excretion of cocaine
  metabolites might be very useful - as far as models go!  :)
  
  I agree that you're not likely to find cocaine but there are several of its metabolites, in addition
  to benzoylecgonine (the most abundant), which are of interest to forensic toxicologists. The purpose
  of the paper cited by Kevin was that ecgonine, compared to other cocaine metabolites, can be
  detected in urine for considerably longer periods. BTW, I'm not so sure about "ethyl or
  propylecgonine" (?) but ecgonine methyl ester is the second most abundant metabolite in urine. Of
  course, if booze was also consumed with the cocaine, the potent metabolite cocaethylene
  (ethylcocaine) would also be found.
  
  - Peter
  
  Peter W. Mullen, PhD, FCSFS
  KEMIC BIORESEARCH (www.kemic.com)
  P.O. Box 878
  Kentville
  Nova Scotia, B4N4H8
  Canada
  
  pmullen.at.kemic.com
  
  

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• On 13 Aug 2013 at 11:10:23, Kevin Bisceglia sent the message
  

  
  Hi All,
  
  I'm a new member writing to ask if it is possible to compute cumulative urinary excretion fractions
  (i.e., percent of administered dose excreted unchanged, as metabolite A, as metabolite B, etc...)
  for a drug and its metabolites knowing only the following information:
  
   - Total dose (mg)
   - Cmax in urine (ng/mL)
   - Tmax in urine (h)
   - Time from administration to last detection (h)
  
  The drug in question is cocaine, and the data comes from this paper:
  
  Smith, M. L., et al., Urinary Excretion of Ecgonine and Five Other Cocaine Metabolites Following
  Controlled Oral, Intravenous, Intranasal, and Smoked Administration of Cocaine J Anal Toxicol (2010)
  34 (2): 57-63 doi:10.1093/jat/34.2.57
  Link: http://jat.oxfordjournals.org/content/34/2/57.long
  
  I don't have urine volumes, concentration-time profiles, or (direct) information about excretion
  rates, so I'm not sure if it can be done.  I guess I could fit the data I have using PK parameters
  that have been published elsewhere, but I assume that the propagated uncertainty would make the
  effort pointless.   However, I am a novice at PK modeling, so please forgive my ignorance.
  
  Thanks in advance for your help,
  --
  Kevin J. Bisceglia, Ph.D.
  Chemistry
  Hofstra University
  Hempstead, NY 11549
  kevin.bisceglia.-at-.hofstra.edu
  
  [You might email/write the authors and ask if they have more details, urine volumes for example -
  db]
  
  

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• On 13 Aug 2013 at 23:04:58, Justin Lutz sent the message
  

  
  Kevin-
  I noticed that this is a repeat request, indicating that you probably didn't receive a satisfactory
  answer initially. I will try and answer your question, but I'm afraid you may not like my answer...
  Urine volume can greatly vary as a function of hydration status and time of day.  Because of this,
  urine drug concentrations have very little meaning without urine volumes.  To determine fraction of
  drug excreted or excretion rate, you ultimately have to determine amount of drug in the urine.
  Without urine volume, I do not believe these parameters are possible to determine.
  Hopefully my response will encourage someone else to prove me wrong ;)
  Good luck.
  -Justin
  
  

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• On 14 Aug 2013 at 09:23:52, Thomas L Tarnowski sent the message
  

  
  Kevin and Justin-
  Sometimes when urine is from healthy subjects and urine creatinine values are known, the assumption
  is made of constant urinary creatinine excretion per time interval, and the drug concentration is
  normalized for creatinine concentration.  But probably not applicable here.
  
  -Tom
  
  Thomas L Tarnowski, Ph.D.
  Bioanalytical Consultant
  ttarnowski1.-a-.aol.com
  
  

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