Published: Journal of Analytical Toxicology, Volume 20, Number 1, January/February 1996, pp. 61.

Significance of Bile Analysis in Drug-Induced Deaths
A. Agarwal and N. Lemos

To the Editor:
Most studies examining the biological distribution of drugs have reported the analyses in blood, liver, brain, and urine (1). Very few studies have reported data on bile. Closer examination of some of these publications revealed that bile had significantly higher concentrations of drugs than blood in almost all cases reported, yet bile is not commonly used as a specimen in routine toxicological analysis. The following is a summary of some of the cases from the literature that reported bile concentrations in addition to blood concentrations. Data for barbiturates and opiates were not included. All three benzodiazepines listed in Table I showed significantly higher concentrations in bile than in blood (2,3). In half of the cases involving diazepam, bile concentrations were even higher than liver concentrations.

In the case of antidepressant drugs (Table II), all drugs showed several-fold higher concentrations in bile than in blood. Drugs such as doxepin, imipramine, trimipramine, sertraline, and norsertraline showed higher concentrations in bile than in liver. For several antidepressant drugs, only one case was found in the literature that reported bile concentrations in addition to blood concentrations, and it is being presented here as such (2,4–9).

All the drugs listed in Table III, including chlorpromazine, thioridazine, ethchlorvynol, methapyrilene, methaqualone, and phenmetrazine, had higher bile concentrations than blood concentrations (2,10–20). In the case of ethchlorvynol, methaqualone, isoniazid, acebutolol, metoprolol, mexiletine, and phenmetrazine, bile concentrations were higher than the liver concentrations. For several of these drugs, only one case was found in the literature that reported bile concentrations in addition to blood concentrations.
Data obtained from the Medical Examiner’s Office on cocaine and three of its metabolites (ecgonine methyl ester, benzoylecgonine, and cocaethylene) are presented in Table IV. In all the cases analyzed, bile concentrations were higher than the blood concentrations for the parent drug, cocaine, as well as for all the metabolites. Liver concentrations were not available. An average of 50 cases indicated that cocaine was present in bile in amounts approximately five times higher than in blood. Ecgonine methyl ester was approximately three times higher than in blood. The average bile concentration of benzoylecgonine was approximately six times higher than its average blood concentration. Cocaethylene was found in bile in amounts seven times higher than in blood. It must be noted that, in several cases, cocaethylene was found negative in blood but was present in bile. This further emphasizes the need to analyze bile as a routine toxicological specimen. If bile samples had not been analyzed, the presence of cocaethylene in several cases would have been missed.
From the information presented here, it is apparent that a routine analysis of bile could prove useful because most drugs are found in bile in significantly higher amounts than in blood. More importantly, those cases in which a drug is not present in blood may not be considered negative for that drug unless a biliary analysis is also performed. A drug present in low concentrations in a system may go undetected if blood is the only specimen analyzed. There is a much smaller chance of this happening if bile is also analyzed. It should also be noted that bile concentrations in several cases were higher than liver concentrations. It has been argued that the presence of drugs in bile indicates only long-term usage. This may be true in cases of acute poisoning, where only a short time has elapsed between drug administration and death and where the drug was not distributed to the tissues. However, in most of the drug distribution cases reported in the literature that also reported data on bile, bile concentrations were higher than the blood concentrations.

Arvind Agarwal and Nikolaos Lemos
John Jay College of Criminal Justice
The City University of New York
445 West 59th Street
New York, NY 10019

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