title: Postmortem femoral blood concentrations of amlodipine.
abstract: Postmortem femoral blood concentrations of the calcium blocker amlodipine were determined by LC-MS-MS and compiled for the years 2003-2010. The cause of death was classified as unrelated to amlodipine in 38 cases in which the concentration ranged from 0.006 to 0.13 mg/kg (median 0.048 mg/kg), a range that exceeds published in vivo therapeutic serum levels by several-fold. In three cases, amlodipine was judged to be a contributing factor to death and concentrations ranged from 0.29 to 0.44 mg/kg. This concentration range is of the same order of magnitude as published serum levels for clinical toxicity cases. One fatality was ascribed to amlodipine poisoning with a concentration of 0.90 mg/kg, which is similar to values observed in previously published fatality cases. One suspected drug-drug interaction case in which the amlodipine level (0.17 mg/kg) was considered elevated due to inhibition of the cytochrome P450 3A4 enzyme by the azole antifungal drug, fluconazole, was detected. In conclusion, it is important to establish postmortem reference concentrations rather than relying on in vivo therapeutic serum levels, which may be too low and lead to false conclusions in postmortem cases.
authors.affiliation: Section of Forensic Chemistry, Dept. of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark. Kristian.linnet@forensic.ku.dk
authors.forename: Kristian
authors.initials: K
authors.lastname: Linnet
authors.forename: Lotte Markussen
authors.initials: LM
authors.lastname: Lang
authors.forename: Sys Stybe
authors.initials: SS
authors.lastname: Johansen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000009:adverse effects / Q000097:blood* / Q000592:standards; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000097:blood* / Q000592:standards; D003933:Diagnosis; D004347:Drug Interactions; D005260:Female; D005263:Femoral Artery / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D012039:Regional Blood Flow
chemical_list: D002121:Calcium Channel Blockers; D017311:Amlodipine