The effect of Mylanta® on naproxen bioavailability was studied in 11 healthy volunteers. In separate experiments, single oral doses of naproxen (250 mg) and multiple oral doses (250 mg twice daily for 7 days) were administered with and without Mylanta. Coadministration of naproxen with Mylanta in the single-dose experiment did not significantly affect the area under the curve (579 vs. 580 μg/ml x hr with and without Mylanta, respectively), time to peak serum concentration (2.5 vs. 2.6 hr), peak serum concentration (37.2 vs. 34.8 μg/ml) or plasma half-life (16.1 vs. 16.4 hr). There was no significant difference between trough level naproxen concentrations at steady state (29.6 μg/ml with Mylanta vs. 30.7 μg/ml without Mylanta). The data were also used to investigate naproxen pharmacokinetics predicted by two different pharmacokinetic models, one of which allowed for protein binding. The nonlinear protein-binding model accurately predicted steady-state concentration, while the values predicted by the linear model exceeded actual values by 33–54%.