Coproxamol (dextropropoxyphene in combination with paracetamol) was implicated in 300-400 deaths from overdose in the UK every year. It was implicated in almost

Paracetamol is rapidly absorbed with peak plasma concentrations occurring within one hour. If taken with food, peak concentrations may be delayed until four hours after ingestion. Paracetamol may be administered orally, intravenously, and rectally. Rectal absorption may be variable. The optimum dose is 1 g with a daily maximum of 4 g. There is, however, no correlation between plasma levels and dose.114

Paracetamol is metabolized and eliminated via three pathways.

1. Approximately 90 percent is conjugated with sulfate or glucuronide. Although the sulfate is less important in adults, it has been proposed as a more active pathway in children, which could account for their greater tolerance to higher doses.

2. Between 5 and 10 percent is metabolized by a cytochrome P-450 mixed function oxidase system. The intermediate metabolite of this pathway, N-acetyl-p-benzoquinoneimine (NAPQI) is detoxified by the addition of sulfhydryl groups. NAPQI has a half-life (t1/2) that is three times longer than that of paracetamol (36 hours versus 12 hours, respectively). This is responsible for the hepatic injury associated with paracetamol toxicity. Normally, glutathione acts as the sulfhydryl group. In nutritionally depleted patients or in the presence of overdose, there may be insufficient glutathione to protect the liver. Renal injury is thought to occur via the same mechanism.

3. Less than 5 percent is eliminated unchanged in the urine. The volume of distribution of paracetamol is 0.75 to 1.0L/kg, with protein binding of 35-50 percent.115

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