Postmortem amlodipine concentrations and postmortem redistribution: a retrospective study of 33 cases.

AIM OF THE STUDY: Amlodipine is a calcium channel blocker used to treat cardiac conditions. At toxic doses, amlodipine can cause death by cardiogenic shock, tissue hypoperfusion and target organ damage. Its pharmacokinetic properties suggest that post-mortem redistribution is possible, precluding interpretation based on living data (plasma concentrations range from 3 to 15 µg/L). Our objective was to determine potentially fatal and non-fatal postmortem amlodipine concentrations.

METHOD: Thirty-three autopsy cases involving postmortem jugular vein blood amlodipine quantification were retrospectively reviewed and classified into two groups based on autopsy findings, regardless of amlodipine dosage results: amlodipine-related or possibly related deaths (G1) and amlodipine-unrelated deaths (G2).Amlodipine concentrations were determined using a validated LC-HRMS method. Groups were compared using a two-tailed Student's t-test.

RESULTS

Of the 33 cases, 16 were classified G1 (median amlodipine concentration 115 µg/L [1st quartile: 85.5; 3rd quartile: 255.5]) and 17 were classified G2 (median amlodipine concentration 41 µg/L [1st quartile: 31; 3rd quartile: 87]) with a statistically significant difference between groups (p = 0.01**). In post mortem whole blood, analyzed by LC-HRMS, concentrations below 90 µg/L (87 µg/L according to our results) appear compatible with non-toxic exposure, whereas concentrations above 250-300 µg/L (255.5 µg/L according to our results) may indicate toxicity contributing to death. In G2, the median amlodipine concentration was 41 µg/L, which is 2.73 times higher than therapeutic concentrations observed in living plasma. The blood/plasma ratio for amlodipine (described as 1.48 or 1.7 depending on the respective reference) does not fully explain the observed difference in concentration in whole blood. Autopsy results involving increased amlodipine concentrations have been described in the literature and may point to the phenomenon of post-mortem redistribution.

CONCLUSION

Postmortem redistribution significantly increases blood amlodipine concentrations compared with therapeutic levels in living subjects, making direct extrapolation unreliable. The distinction between non-toxic and potentially toxic concentrations is essential for forensic interpretation. Further large-scale, multicenter studies are warranted to establish validated postmortem reference ranges for this medication.