Evaluating suspected co-proxamol overdose

In three instances of suicidal poisoning by co-proxamol (paracetamol and dextropropoxyphene) blood samples were obtained from 11 sites together with eight tissue samples, bile, urine, gastric contents and duodenal contents. Site-dependent differences in blood propoxyphene concentration varied between the three cases but concentrations were consistently lowest in peripheral blood and highest in central sites: 3.9-5.5 (pulmonary vein) mg/l; 4.6-25 (pulmonary vein) mg/l; 3.2-40 (aorta) mg/l. There was a less than twofold variation in corresponding blood paracetamol concentrations. Reference data on fatal propoxyphene blood concentrations do not specify the blood sampling site and can be misleading. The intra-individual variability of propoxyphene concentrations in blood in these three cases underscores this problem. Tissue concentrations of propoxyphene showed considerable inter-individual variability in degree and pattern. Tissue concentrations of paracetamol showed a less than twofold intra-individual variation. Body drug loads were calculated by two methods: from organ weights and tissue concentrations; from published volume of distribution data (Vd). For paracetamol the body drug load is underestimated by the organ weight calculation but the Vd calculation approximates the suspected dose based on anamnestic information. For propoxyphene the body drug load is seriously underestimated by the organ weight calculation and overestimated up to 2.5 times by the Vd calculation. Since the two drugs have a fixed ratio in co-proxamol then the dose of propoxyphene (the effective lethal agent) can be inferred from the paracetamol dose calculated by Vd. This approach may be applicable to cases of overdose with other compounded drug preparations.