Markedly altered colchicine kinetics in a fatal intoxication: Examination of contributing factors

Abstract

1 Colchicine poisoning, which is relatively rare, is associated with significant morbidity and mortality. Whilst a new treatment modality, in the form of colchicine-specific Fab fragments is on the horizon, currently available therapy is largely supportive. 2 The elimination of colchicine occurs primarily by hepatic metabolism, following a first-order process, with significant enterohepatic circulation. Renal extraction is responsible for approximately 20% of colchicine elimination. 3 We report a case of colchicine intoxication, compli cated by the presence of co-ingestants, in which serum colchicine concentrations remained quasi-constant over the 3 days of the patient's survival, consistent with marked alterations both in metabolism and excretion. The initial presentation was relatively benign but the subsequent course was one of severe colchicine poisoning, resulting in death. 4 Severe colchicine toxicity appears to have resulted in a vicious cycle of progressive organ dysfunction and impaired elimination. 5 Josamycin, one of the co-ingestants and an inhibitor of P-glycoprotein, the membrane pump responsible for multidrug resistance, may have played a significant role in impeding the cellular and biliary elimination of colchicine. Co-ingested opioid and anticholinergic compounds may have altered colchicine absorption and gastrointestinal transit. 6 This case serves as a reminder of the need for attention to co-ingested drugs, to early aggressive therapy, and if available, to consideration of immunotherapy.