Kinetics of acetaminophen after single- and multiple-dose oral administration as a gradient matrix system to healthy male subjects

The in vivo characteristics of two formulations of a recently developed controlled‐release system, the Gradient Matrix System (GMS‐1 and GMS‐2), with acetaminophen as a model drug compound have been determined in healthy volunteers both after separate single‐ and multiple‐dose administration. Values for the mean residence time (MRT) were increased from 5·2 h for an oral solution to 10·2 and 13·3 h for two GMS formulations after single dosing. Peak plasma concentrations were lower for the two GMS formulations after single dosing compared to the oral solution. The bioavailability, relative to the oral solution, was 91 per cent and 84 per cent for the two GMS formulations tested. After multiple dosing of one of the GMS formulations over 5 days, no change in AUC compared to the single dose AUC occurred. Steady state was reached within 2–3 days of twice daily dosing of the GMS formulation. The peak‐trough‐fluctuation (per cent PTF) was 44 per cent. No signs of dose dumping were observed in fasted subjects. A plateau‐like plasma drug concentration profile at steady state was maintained with the GMS formulation.