|SOFT - TIAFT 1998||Poster Session 3||Thursday October 8, 1998|
LIMITATIONS IN THE USE OF PHARMACOKINETIC CALCULATIONS FOR FORENSIC TOXICOLOGY|
Ines B. Collison
Orange County Sheriff-Coroner Department, Forensic Science Services 320 North Flower, Santa Ana, California 92703 USA
|Pharmacokinetic retrograde calculations and total body-burden calculations are a common request in the field of forensic toxicology. Although theoretically appropriate, biological, pharmacological and toxicological considerations, in addition to postmortem changes make such calculations inaccurate, limiting their application. Two recent cases from our laboratory support that conclusion:
Case 1: A 52 month-old boy, who weighed 17.2 kg, and his 28 month-old sister, who weighed 14.5 kg, were found dead, suffocated. The suspect confessed to having given Dimetapp Elixir TM (brompheniramine (brphen) and phenylpropanolamine (PPA) to the victims some time before the incident. The postmortem concentration of PPA and brphen were 2.17 and 0.17 mg/L and 1.87 and 0.15 mg/L for the boy and girl respectively. Both the prosecution and the defense became interested in determining the "total amount of Dimetapp given to the victims" and its dose equivalence. The volume of distribution (Vd) of brphen reported in the literature is 11.7 + 3.1 L/kg and the Vd of PPA for children 6 to 12 years old, weighing 20 to 40 kg is 2.5 + 0.3 and 2.8 + 0.4 L/kg depending on the dose. The recommended doses of brphen and PPA for children 2 to 6 years old are 0.73 mg and 5.0 mg respectively. Using pharmacokinetic parameters, it was estimated that the amount of PPA given to the boy was 16 to 24 times higher than recommended and the amount of brphen 34 to 59 times higher than recommended. The amount of PPA estimated to have been given to the girl was 12 to 17 times higher than recommended and the amount of brphen 26 to 44 times higher than recommended.
Case 2: A 17-year old female was involved in a stressful domestic situation. She was found disoriented, pale and feverish, and was taken to the emergency room where she died 3 hours later, approximately 12 hours after ingesting an unknown amount of acetaminophen and aspirin. The postmortem blood salicylate and acetaminophen levels were 0.86 and 0.48 mg/L respectively. Her clinical history is consistent with hepatotoxic effects of acetaminophen. Due to insistent family requests, pharmacokinetic calculations were made. The results suggest the dose of acetaminophen taken by the decedent to be between 106 and 337 kg, while the dose of salicylate could vary between 14 g and 6.2 x108 kg.