Gliclazide
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Hypoglycaemia following inappropriate drug use: case report A 46-year-old woman died of hypoglycaemia following inappropriate use of gliclazide for type 2 diabetes mellitus. The woman was found in unconscious state at home in France by her husband. Later, she was declared as dead, and her prosecutor requested an autopsy and toxicological investigations. Three days after the death, an autopsy findings revealed normal heart with little atheromatous plaque in the coronaries without calcification, generalised organ congestion without any traumatic injury. Histology revealed pulmonary oedema. Non-specific congestion of the kidney and liver was also observed. These findings showed multi viscera congestion, labial ecchymosis, moderate cerebral oedema and asphyxia syndrome. During the autopsy, femoral blood, cardiac blood, hair, gastric content and vitreous fluid were collected and stored for further toxicological investigations. Two days later, the medical staff came to know that she had been receiving modified release tablets of gliclazide [Diamicron] for type 2 diabetes [dosage not stated]. The autopsy findings were consistent with a possible fatal hypoglycaemia. There was a delay of 6 weeks between specimen collection after death and toxicological analysis due to administrative and legal formalities. Therefore, tests to measure insulin, glucose, C-peptide, lactate or other biochemical parameters of hypoglycaemia were not performed. Toxicological screening included gliclazide, ethanol, carboxyhaemoglobin, volatiles, cyanides and ELISA tests to detect pharmaceuticals and drugs of abuse. Ethanol tested negative in the vitreous fluid and blood whereas γ-hydroxybutyric acid and cyanides were within normal range in the blood specimen. ELISA test was negative for abuse of drugs and pharmaceuticals. Her carboxyhaemoglobin was 0.6%. The screening of the all collected specimens tested positive for gliclazide. The concentration in the blood was in the range of therapeutic concentrations. On the basis of the blood gliclazide level, there was no evidence of gliclazide post-mortem redistribution. The very low drug levels in the gastric content suggested drug administration several hours prior to death with complete absorption. Based on the autopsy findings, a pathologist considered three possible causes of death: natural or traumatic cause, gliclazide overdose and gliclazide-induced fatal hypoglycaemia due to treatment non-compliance. According to the pathologist, traumatic cause was excluded as there was no signs of organ failure or trauma during the autopsy. The gliclazide overdose was suspected. Therefore, gliclazide stability testing was performed on the blood sample that was stored at +4°C for 6 weeks. The stability analysis indicated the presence of 35% of gliclazide. However, these findings were irrelevant for overdose and back-calculation of the drug concentration in the victim’s blood at the time of death could not be measured as various factors could influence the final drug concentration. Therefore, the pathologist e
