PHARMACOKINETICS OF ORAL DECONGESTANTS

Only three drugs are commonly used as oral decongestants-phenylpropano lamine (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 a nd PDE are readily and completely absorbed, whereas PE, with a bioavai lability of only approximately 38%, is subject to gut wall metabolism and is thought to be absorbed erratically. Peak concentrations are rea ched 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 hum ans are available. Whereas PPA and PDE are not substantially metaboliz ed, PE undergoes extensive biotransformation in the gut wall and the l iver. Elimination of PPA and PDE is predominately renal, with urinary excretion being pH dependent. Half-lives are relatively short, approxi mately 2.5 hours for PE, 4 hours for PPA, and 6 hours for PDE. Elimina tion 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 mo noamine oxidase inhibitors. No direct relationship between nasal decon gestant effect and plasma concentration has been established.