Tomson T, Sköld A C, Holmgen P, Nilsson L, Danielsson B
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
Ther Drug Monit. 1998 Jun;20(3):309-12. doi: 10.1097/00007691-199806000-00011.
Observations of low postmortem blood concentrations of antiepileptic drugs in cases of sudden unexpected death in epilepsy (SUDEP) have led to the assumption that noncompliance may play a role in SUDEP. However, the reliability of postmortem drug levels has been questioned. The purpose of this study was to analyze possible postmortem changes in blood concentrations of carbamazepine (CBZ) and phenytoin (PHT). New Zealand white rabbits were fed with PHT or CBZ until assumed steady state. A blood sample was then drawn for determination of serum and whole blood concentrations of CBZ and PHT, after which the rabbits were killed and stored at 6 degrees C. A further blood sample for drug analysis was obtained 72 hours after death. Antemortem serum concentrations of CBZ were not significantly different from whole blood concentration 72 hours after death. In contrast, antemortem whole blood concentrations of PHT were only 65% of the corresponding serum concentrations, and postmortem PHT blood levels were even lower, being 35% of antemortem serum concentrations. In conclusion, blood concentrations of CBZ seem to be stable during 72 hours after death under these experimental conditions. However, postmortem PHT concentrations should be interpreted with caution and low postmortem concentrations do not necessarily imply a poor compliance.
在癫痫性猝死（SUDEP）病例中，观察到死后血液中抗癫痫药物浓度较低，这使得人们认为不遵医嘱可能在SUDEP中起作用。然而，死后药物水平的可靠性受到了质疑。本研究的目的是分析卡马西平（CBZ）和苯妥英（PHT）血液浓度可能的死后变化。给新西兰白兔喂食PHT或CBZ直至假定达到稳态。然后采集一份血样以测定CBZ和PHT的血清及全血浓度，之后处死兔子并储存在6摄氏度。死后72小时获得另一份用于药物分析的血样。死后72小时，CBZ的生前血清浓度与全血浓度无显著差异。相比之下，PHT的生前全血浓度仅为相应血清浓度的65%，死后PHT血液水平甚至更低，为生前血清浓度的35%。总之，在这些实验条件下，CBZ的血液浓度在死后72小时似乎是稳定的。然而，对死后PHT浓度的解读应谨慎，死后浓度低并不一定意味着依从性差。
