Steady-state human pharmacokinetics and bioavailability of guaifenesin and pseudoephedrine in a sustained-release tablet relative to immediate-release liquids

Steady-state human pharmacokinetics and bioavailability were compared for a sustained-release decongestant/ expectorant tablet and two coadministered immediate-release liquids that together contained the same active ingredients. In each leg of a randomised, two-leg, complete crossover, multiple-dose study, 15 of the 30 enrolled healthy male subjects received Entex® PSE (600 mg guaifenesin (GGE) and 120 mg pseudoephedrine hydrochloride (PSE HCl) in a matrix formulation) twice daily on days 1-4 and once daily on day 5. The remaining subjects received the reference dose forms, Robitussin® (300 mg GGE/15 ml) and Sudafed® (60 mg PSE HCl/10 ml) immediate-release liquids, coadministered four times daily on days 1-4 and twice daily on day S. Plasma GGE and PSE pharmacokinetic data indicated that steady state was attained by day 5 of dosing for both the tablet and the reference liquids. The sustained drug release from Entex PSE resulted in a significant (P = 0.0001) reduction in the GGE fluctuation index (as C(max) minus C(min) divided by the average plasma drug concentration) and no difference in the PSE fluctuation index as compared with the corresponding indexes for the reference liquids. Under steady-state conditions, sustained-release GGE and PSE profiles were obtained for Entex PSE. The extents of GGE and PSE absorption were equivalent for the tablet and coadministered immediate-release liquids, and no dose dumping occurred with the sustained-release dosage form.