Pregabalin concentrations: establishing 'normal' and 'cause for concern' concentration ranges in postmortem blood

Area of Science:

• Forensic Toxicology
• Pharmacology
• Clinical Chemistry

Background:

• Pregabalin (PGL) is widely prescribed but also subject to misuse, often at supra-therapeutic doses.
• Determining the contribution of PGL to postmortem findings is challenging due to individual variability and postmortem changes.
• Meaningful postmortem (PM) data for interpreting PGL concentrations in femoral-vein blood are scarce.

Purpose of the Study:

• To establish reference ranges for PGL concentrations in postmortem femoral-vein blood across all manners of death.
• To provide toxicologists with data to differentiate between incidental PGL findings and concentrations potentially related to cause of death.
• To propose a concentration cut-off for PGL in postmortem blood that warrants further investigation.

Main Methods:

• Analysis of PGL concentrations in femoral-vein blood from postmortem cases over a 2-year period.
• Inclusion of cases from all manners of death to ensure comprehensive data.
• Statistical analysis to determine concentration ranges and identify a significant cut-off value.

Main Results:

• A recommended cut-off concentration of ≥20 µg/mL for PGL in postmortem femoral-vein blood is proposed.
• PGL concentrations ≤19 µg/mL may be considered incidental, though other factors like tolerance and co-ingested drugs are important.
• This study provides crucial reference data for toxicological interpretation of PGL levels in postmortem investigations.

Conclusions:

• A PGL concentration of ≥20 µg/mL in postmortem femoral-vein blood should be considered significant and a potential 'cause for concern'.
• Concentrations below 20 µg/mL may represent 'normal' incidental findings, but require contextual interpretation.
• The findings aid toxicologists in assessing the role of PGL in postmortem cases, improving accuracy in death investigations.