Fatal poisoning case involving drug interaction due to the inhibition of cytochrome P450

Abstract

Background/Aim. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of various drugs and chemicals. Forensic pathologist should consider not only pharmacodynamic interactions by multiple drugs, but also the pharmacokinetic drug interactions of each drug in casework of multiple drug ingestion. Case report. A female in her forties, receiving therapy for alcohol dependence, was found dead in her house.Medico-legal autopsy revealed no findings suggestive of natural disease. Quantitative toxicological analysis showed that levomepromazine, promethazine, dextromethorphan, estazolam, clomipramine, risperidone, and flunitrazepam concentrations in femoral blood were 0.750 µg/mL, 0.701 µg/mL, 0.332 µg/mL, 0.390 µg/mL, 0.216 µg/mL, 0.031 µg/mL, and 0.002 µg/mL, respectively, along with a blood ethanol level of 377 mg/dL. Conclusion. We concluded that the cause of death was interaction between ethanol and multiple psychotropic drugs. Pharmacokinetic drug interactions due to the inhibition of CYPs should be considered in the evaluation of toxicity in poisoning cases involving multiple drugs. Key words: drug interaction; overdose; levomepromazine; cytochrome P450 (CYP); dextromethorphan. Apstrakt Uvod. Enzimi P450 (CYP) su odgovorni za metabolizam različitih lekova i hemikalija. Forenzički patolog treba da razmotri ne samo farmakodinamske interakcije više lekova već i farmakokinetičke interakcije svakog leka u slučaju multiple ingestije lekova. Prikaz bolesnika. Žena 40-ih godina, na lečenju od zavisnosti od alkohola, nađena je mrtva u svojoj kući. Medikolegalnom autopsijom nisu nađeni zanci koji bi upućivali na prirodnu bolest. Kvantitativnom toksikološkom analizom nađeno je da su koncentracije levomepromazina, prometazina, dekstrometorfana, estazolama, klomipramina, risperidona i flunitrazepama u femoralnoj krvi bile: 0.750 µg/mL, 0.701 µg/mL, 0.332 µg/mL, 0.390 µg/mL, 0.216 µg/mL, 0.031 µg/mL, and 0.002 µg/mL, redom, uz etil alkohol u krvi u koncentraciji od 377 mg/dL. Zaključak. Zaključili smo da je uzrok smrti bila interakcija između etil alkohola i više psihotropnih lekova. Farmakokinetičke interakcije lekova zbog inhibicije CYP-a treba da budu razmotrene u proceni toksičnosti kod slučajeva trovanja koji uključuju više lekova. Ključne reči: interakcija lekova, overdoza, levomepromazin, citohrom P450 (CYP), dekstrometorfan.