Dose dependent pharmacokinetics of N-acetylcysteine after oral dosing to man

The pharmacokinetics after oral administration of 200, 600 or 1200 mg of N-acetylcysteine (NAC) were studied in 10 healthy subjects. Normalized maximal plasma concentration was significantly higher after a 600 mg dose than after a 200 mg dose. Bioavailability of NAC significantly increased with increasing dose. Time for maximal plasma concentration also increased with increasing dose. The observations can be explained by a capacity-limited presystemic elimination of NAC. In an extension of the study, 600 mg of NAC was given twice a day for 5 days and the plasma concentrations were followed after the morning dose on day 6. No differences in the pharmacokinetic parameters were observed in comparison with the single 600 mg dose. This indicates that the beneficial clinical effects observed after repeated dosing can not be ascribed to an accumulation of NAC in plasma.