Pharmacokinetics of oral acetylcysteine: absorption, binding and metabolism in patients with respiratory disorders.

ABSTRACT

The fate of an oral 100 mg dose of 35S-acetylcysteine, a mucolytic agent, was studied in 10 patients with respiratory disorders, 5 of whom underwent pneumonectomy or lobectomy a few hours after administration of the drug. In the 5 nonoperated patients, plasma radioactivity concentrations were maximal after 2 to 3 hours and remained high after 24 hours; about 22% of radioactivity was excreted in urine after 24 hours. In the 5 operated patients, plasma radioactivity concentrations were comparable with those in the nonoperated patients. Lung tissue radioactivity concentrations after 5 hours were comparable with those in plasma, while the presence of small amounts of radioactivity in the bronchial secretions indicates that acetylcysteine passes into the mucus. Total radioactivity after 5 hours consisted of free, unchanged drug and metabolites (about 22% of total in plasma, 48% in lung tissue), unchanged drug bound to protein by means of labile disulphide bridges (about 14% in plasma, 47% in lung tissue), and drug firmly bound to protein (about 64% in plasma, 5% in lung tissue). Oral acetylcysteine is rapidly absorbed and slowly excreted and is available in the lung in an active form for at least 5 hours at high concentrations.