Pharmacokinetics of oral decongestants

Abstract

Only three drugs are commonly used as oral decongestants--phenylpropanolamine (PPA), pseudoephedrine (PDE), and phenylephrine (PE). They are all chiral drugs that exist as stereoisomers. It is possible that each enantiomer can reflect significant enantioselective differences with regard to both pharmacokinetic and pharmacodynamic effects. Both PPA and PDE are readily and completely absorbed, whereas PE, with a bioavailability of only approximately 38%, is subject to gut wall metabolism and is thought to be absorbed erratically. Peak concentrations are reached between 0.5 and 2 hours after administration. All three drugs are extensively distributed into extravascular sites (apparent volume of distribution between 2.6 and 5.0 L/kg). No protein-binding data in humans are available. Whereas PPA and PDE are not substantially metabolized, PE undergoes extensive biotransformation in the gut wall and the liver. Elimination of PPA and PDE is predominantly renal, with urinary excretion being pH dependent. Half-lives are relatively short, approximately 2.5 hours for PE, 4 hours for PPA, and 6 hours for PDE. Elimination of PPA and PDE may be rapid in children, and the agents should be used with caution in patients with renal impairment. In addition, PPA increases caffeine plasma levels and decreases theophylline clearance. Reduced metabolism of PE occurs with concurrent administration of monoamine oxidase inhibitors. No direct relationship between nasal decongestant effect and plasma concentration has been established.