Just say no to postmortem drug dose calculations

Area of Science:

• Forensic Toxicology
• Clinical Pharmacology
• Pharmacokinetics

Background:

• Professional groups have long cautioned against calculating administered drug doses from postmortem blood concentrations.
• Limited empirical data exists on the unreliability of these postmortem dose estimations.

Purpose of the Study:

• To quantify the unreliability of calculating administered drug doses from postmortem blood concentrations.
• To assess the accuracy and precision of dose estimations using amitriptyline as a model drug.

Main Methods:

• Utilized empirically determined pharmacokinetic variables for amitriptyline from clinical studies.
• Incorporated data from clinical overdoses (survived) and fatal amitriptyline toxicity cases with known doses.
• Applied standard pharmacokinetic equations and error propagation to estimate dose accuracy.

Main Results:

• Calculated doses showed extreme inaccuracy, with mean errors ranging from +128% to +2347%.
• Precision was also very poor, with standard deviations from ±383% to ±3698%.
• These wide error margins preclude reliable estimation of consumed doses from postmortem blood concentrations.

Conclusions:

• Dose calculations based on postmortem blood drug concentrations are fundamentally unreliable.
• This study reinforces existing warnings against using such methods in forensic and clinical toxicology.
• The findings highlight the need for alternative methods in postmortem drug analysis.