Pharmacokinetics
By Kevin Shanks, D-ABFT-FT
Pharmacokinetics (PK) is the study of what the body does to a substance. The word is derived from Greek – Pharmakon which means “drug” and kinetikos which means “moving”. PK consists of four areas – absorption, distribution, metabolism, and excretion. This is also known as ADME.
Absorption (A) is the process by which substances enter the bloodstream. Substances can enter the bloodstream through a wide variety of routes, including oral (by mouth), inhalation (lungs), intravenous (injected into a vein), intramuscular (injected into muscle), rectal (suppository), oral mucosa (under the tongue), intrathecal (spinal fluid), dermal (skin), ocular (eye), and intranasal (nose).
Distribution (D) refers to the transfer of a substance form one part of the body to another. When discussing PK, this usually refers to the movement of substance from the blood into the tissues of the body (liver, heart, kidney, brain, muscle, and fat). Some factors that influence distribution are lipophilicity, pH, and plasma protein binding.
Metabolism (M) is the process by which the substance is altered to facilitate the removal of it from the body. Most metabolism occurs in the liver, but it can also occur in the kidneys, lung, gastrointestinal tract, and blood. Examples of metabolism include deacetylation (heroin to 6-acetylmorphine to morphine), nitro reduction (clonazepam to 7-aminoclonazepam), N-dealkylation (amitriptyline to nortriptyline), deamination (chlordiazepoxide to demoxepam to nordiazepam), and ester hydrolysis (cocaine to benzoylecgonine), as well as glucuronidation (oxazepam to oxazepam glucuronide), sulfate formation (morphine to morphine sulfate), and glycine conjugation (salicylate to salicyluric acid)
Excretion (E) is the final removal of the substance or by products from the body. Excretion is most commonly done via the liver and kidneys, but can occur via the lungs, breast milk, feces, sweat, sebum, and semen.
PK can help answer questions such as ‘Are drugs involved in this incident?’, ‘How much substance did a living individual consume?’, or ‘When was a substance taken by an individual?’.
The larger question at hand in many cases regarding impairment, drug toxicity, or a substance’s role in cause of death involves a related area of pharmacology called pharmacodynamics (PD), which will be explored in a later blog post.
If you have any questions or concerns regarding the role of pharmacokinetics in your toxicology case, please reach out to our Axis Forensic Toxicology subject matter experts at [email protected].
References
Guidelines for the Interpretation of Analytical Toxicology Results. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages xxx-xlii. (2020).
Pharmacokinetics and Pharmacodynamics. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. American Association for Clinical Chemistry (AACC). 2017. 77-93.
Introduction to Forensic Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 1-12. (2008).
Postmortem Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 191-218. (2008).
Postmortem Forensic Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 3-14. (2017).
Alcohol, Drugs, and Driving. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 299-322. (2008).
Human Performance Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 15-30. (2017).
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Postmortem Redistribution
by Kevin Shanks, M.S., D-ABFT-FT
Postmortem redistribution (PMR) is the phenomenon that occurs in blood drug concentrations after death as drug from anatomic sites of high drug concentration (e.g. organs such as the liver, lungs, and heart (myocardium)) is released to sites of lower drug concentration (e.g. the blood). This release may falsely elevate the drug concentration in blood surrounding the organs or from the central cavity.
Substances that are alkaline (pH > 7.0), lipophilic, and have volumes of distribution (Vd) greater than 3 L/kg are more likely to undergo PMR. These substances include many commonly detected drugs such as tricyclic antidepressants (e.g. amitriptyline, nortriptyline), amphetamines (e.g. methamphetamine, amphetamine), and opioids (e.g. fentanyl, oxycodone).
The exact mechanism of PMR has not yet been identified, but changes in pH and protein structure after death are thought to also play a role in the phenomenon. Because of this phenomenon, the preferred anatomical sites of blood collection for toxicological analyses are peripheral sites such as the iliac or femoral veins. The site of blood collection is but one variable in the occurrence of PMR. Other factors influencing PMR include body storage temperature (the higher the temperature, the greater the potential for concentration change), the time between death and specimen collection (a longer lapsed time gives more potential for changes), the position of the body when found (blood may drain from centrally located sites to peripherally located sites), and medical intervention (stomach contents may be aspirated or blood may move from central to peripheral sites; drug may be released from traumatized tissue into blood).
Even as it has been studied for decades, PMR is a complex process and is still not fully understood, but the aforementioned factors are just some variables to be considered when interpreting toxicology’s role in a medical-legal death investigation.
If you have any questions or concerns regarding PMR’s role in a postmortem toxicology case, please reach out to our Axis Forensic Toxicology subject matter experts at [email protected].
References
- Barnhart FE, Bonnell HJ, Rossum KM. Postmortem Drug Redistribution. Forensic Sci Rev. 2001. Jul;13(2):101-129.
- Pelissier-Alicot AL, Gaulier JM, Champsaur P, Marquet P. Mechanisms Underlying Postmortem Redistribution of Drugs: A Review. J Anal Toxicol. 2003 Nov-Dec;27(8):533-544.
- Yarema MC, Becker CE. Key Concepts in Postmortem Drug Redistribution. Clin Toxicol (Phila). 2005;43(4):235-241.
- Postmortem Redistribution of Drugs. Principles of Forensic Toxicology. Fifth Edition. Fred S. Apple, Barry S. Levine, Sarah Kerrigan. Springer Nature Switzerland AG. 2020. 595-602.
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The Realms of Forensic Toxicology
By Kevin Shanks, M.S., D-ABFT-FT
Toxicology is the study of the effects of substances on living organisms. Forensic toxicology is the use of toxicology in medical-legal investigations. Forensic toxicologists use analytical chemistry, pharmacology, and clinical chemistry to aid in these investigations of death, poisoning, intoxication, or substance use.
The field of forensic toxicology can be broken down into three main realms: postmortem toxicology, human performance toxicology, and forensic drug testing.
Postmortem toxicology is the analysis of biological specimens obtained at autopsy in order to identify the effect of drugs or poisons. These biological specimens may include blood, urine, vitreous humor, bile, gastric contents, and tissues such as liver, kidney, spleen, and brain. The toxicological analyses and toxicologist’s expertise aid in the certification of cause and manner of death, which is determined by the forensic pathologist, medical examiner, or coroner.
Human performance toxicology is the analysis of biological specimens obtained by a hospital or law enforcement agency in order to identify the effects of drugs on psychomotor performance. The typical biological specimen analyzed is whole blood, but may also include blood serum, blood plasma, or in some case, urine. The toxicological analyses and toxicologist’s opinion, in conjunction with observed witness reports and field tests administered by law enforcement officials, help in the determination if a person is under the influence of a substance during a specific incident, such as a motor vehicle stop or collision.
Forensic drug testing is the analysis of biological specimens obtained by a physician, hospital system, the criminal justice system, the public business sector (e.g. Department of Transportation, etc.) and private workplaces or businesses to identify substance use. The primary specimen used in forensic drug testing is urine, but other specimens analyzed include oral fluids, hair, and sweat. The presence or absence of substances detected in biological specimens along with the toxicologist’s scientific opinion, after review of case circumstances and context, allow for the decision to be made regarding potential substance use.
Common instrumentation used across all three realms of forensic toxicology includes immunoassay, gas chromatography with mass spectrometry (GC-MS), and liquid chromatography with mass spectrometry (LC-MS). Routine drugs monitored in all realms include amphetamine, methamphetamine, cocaine, heroin, fentanyl, prescription opioids, PCP, barbiturates, cannabis, and ethanol. The scope of analysis can change to include a more comprehensive scope (e.g. designer opioids, synthetic cannabinoids, novel psychoactive substances, etc.) according to the case circumstances and specifics.
To stay current with the scope of testing for all realms of toxicology offered by Axis Forensic Toxicology, please consult the online test catalog.
- Order Code 70530, Drugs of Abuse Panel, Blood
- Order Code 70510, Comprehensive Drug Panel, Blood
- Order Code 70080, Drugs of Abuse Panel, Urine
- Order Code 13810, Designer Opioids Panel, Blood
- Order Code 42130, Synthetic Cannabinoid Panel, Blood
- Order Code 13610, Psychoactive Substances Panel, Blood
References
Guidelines for the Interpretation of Analytical Toxicology Results. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages xxx-xlii. (2020).
Introduction to Forensic Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 1-12. (2008).
Postmortem Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 191-218. (2008).
Postmortem Forensic Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 3-14. (2017).
Alcohol, Drugs, and Driving. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 299-322. (2008).
Human Performance Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 15-30. (2017).
Workplace Drug Testing. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 135-152. (2008).
Forensic Drug Testing. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 31-48. (2017).
Drug Facilitated Sexual Assault. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 287-298. (2008).
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