MARKEDLY ALTERED COLCHICINE KINETICS IN A FATAL INTOXICATION - EXAMINATION OF CONTRIBUTING FACTORS

1 Colchicine poisoning, which is relatively rare, is associated with s ignificant morbidity and mortality. Whilst a new treatment modality, i n the form of colchicine-specific Fab fragments is on the horizon, cur rently available therapy is largely supportive. 2 The elimination of c olchicine occurs primarily by hepatic metabolism, following a first-or der process, with significant enterohepatic circulation. Renal extract ion is responsible for approximately 20% of colchicine elimination. 3 We report a case of colchicine intoxication, complicated by the presen ce 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 o f severe colchicine poisoning, resulting in death. 4 Severe colchicine toxicity appears to have resulted in a vicious cycle of progressive o rgan dysfunction and impaired elimination. 5 Josamycin, one of the co- ingestants and an inhibitor of P-glycoprotein, the membrane pump respo nsible for multidrug resistance, may have played a significant role in impeding the cellular and biliary elimination of colchicine. Go-inges ted opioid and anticholinergic compounds may have altered colchicine a bsorption and gastrointestinal transit. 6 This case serves as a remind er of the need for attention to co-ingested drugs, tb early aggressive therapy, and if available, to consideration of immunotherapy.