Comparison between premortem and postmortem serum concentrations of phenobarbital, phenytoin, carbamazepine and its 10,11-epoxide metabolite in institutionalized patients with epilepsy

The last premortem serum concentrations of phenobarbital (PB), phenytoin (P HT), carbamazepine (CBZ) and its CBZ-10,ll-epoxide metabolite (CE) were com pared with the corresponding postmortem serum concentrations in 16 adult pa tients of an epilepsy centre. Based on complete postmortem examinations, 12 individuals showed a known cause of death (KCD) and four patients succumbe d from sudden unexplained death (SUD). The last premortem and the postmorte m serum levels of PB (r = 0.991), PHT (r = 0.986), CBZ (r = 0.985) and CE ( r = 0.936) were highly correlated. However, the regression analysis indicat ed that, except for CE, the premortem concentrations were significantly hig her than the postmortem concentrations, i.e. 65% for PB, 34% for PHT, and 1 6% for CBZ. Varying time lapses (4-62 h) between death and serum sampling d uring autopsy did not significantly influence the ratio of premortem to pos tmortem serum levels for PB, PHT? CBZ, and CE (p > 0.1). Furthermore we fou nd no significant differences between the premortem and the postmortem seru m concentration ratios CE/CBZ. Considering the above variables, the data of SUD and KCD patients were comparable. Postmortem decrease in anticonvulsan t serum concentrations, especially for PB and PHT, should be considered in order to avoid misinterpretation in respect to so-called 'subtherapeutic' s erum levels and noncompliance in context with SUD or fatal intoxication. (C ) 1999 Elsevier Science B.V. All rights reserved.