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

Pregabalin (PGL) is prescribed for the treatment of neuropathic pain, epilepsy, and general anxiety disorder; however, studies have shown that PGL is being misused. It is generally accepted that those who misuse PGL use it in amounts significantly greater than the recommended therapeutic dose. In some instances, such high doses may be well tolerated, and in some instances, the same dose may cause death. Individual variation and postmortem (PM) changes make it extremely challenging for toxicologists to determine if a drug concentration found at PM was contributory to death or not. Unfortunately, meaningful PM data, which can help with interpreting PGL concentrations in femoral-vein blood, are rare. Only one recommendation was found where an author suggested that a PGL concentration of >25 mu g/mL in PM blood should be considered as significant; however, in this case series PGL was only screened for in specific cases. To aid interpretation of PGL concentrations, reference data from toxicological analysis conducted on femoral-vein blood only from all manners of death are needed to compile meaningful and unbiased concentration ranges. This study looked at PGL femoral-vein blood concentrations in PM cases from all manners of death over a 2-year period. As it is impossible to define a PM concentration that should be considered toxic/fatal, this study aimed to provide a concentration cut-off where the PGL may be considered a 'normal' incidental finding (unlikely to be the cause of death) or a 'cause for concern' where it may have been taken in excess and caused or contributed to death. This study recommends that a PGL concentration of >= 20 mu g/mL in femoral-vein blood should be considered as significant and a 'cause for concern'. Concentrations of <= 19 mu g/mL may be considered a 'normal' incidental finding in death, but tolerance and other drug findings need to be considered.