SK&F 93319, a potent histamine H1- and H2-receptor antagonist, is rapidly absorbed with a low rate of plasma clearance primarily by metabolism. Excretion is divided evenly between urine and faeces (probable biliary elimination) with little unchanged drug in the urine. Serum protein binding at low concentrations is very extensive and appears to restrict distribution of SK&F 93319. At higher concentrations (higher dose levels) reduced protein binding results in a marked proportional increase in available free drug with a consequent increase in distribution and clearance. Bioavailability is reduced at higher dose levels. The importance of factors contributing to non-linear pharmacokinetics and the potential clinical consequences are demonstrated.
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