Dehydration, secondary to fever, vomiting and hyperpnea may be severe. Aspirin and aspirin containing products are well absorbed after therapeutic doses given orally. Overdose conditions often delay absorption with peak salicylate levels not being seen until 24 hours after ingestion. Alteration of protein binding sites, through competition with other highly bound substances or saturation of binding sites in overdose, will increase unbound or toxicologically active salicylate concentrations. Free salicylate is then able to penetrate tissues and exert toxic effects.
Acidemia increases the volume of distribution by facilitating salicylate tissue penetration.
In small doses, most salicylate is metabolized in the liver by conjugation with small amounts being hydroxylated. These pathways become saturated at higher doses prolonging salicylate elimination. Conjugated and hydroxylated metabolites are readily excreted by the kidney. Renal elimination is responsible for the majority of salicylate elimination in overdose. An alkaline urine will promote salicylate elimination by decreasing renal tubular reabsorption while an acid urine will retard excretion by promoting reabsorption of salicylate by the kidney tubules.