Steady state pharmacokinetics of naproxen in young and elderly healthy volunteers

Abstract

The pharmacokinetic properties of naproxen (375 mg twice daily and 750 mg twice daily) were evaluated in 23 young (age range, 19 to 32 years) and 25 elderly (age range, 65 to 74 years) healthy male volunteers. After an initial screening examination, each subject received 15 doses of naproxen in this double-blind parallel study. Comparison of trough plasma naproxen concentrations (12 hours after each of the last two morning doses) verified steady state and provided no evidence of drug accumulation in either age or dosage group beyond that achieved after seven days of naproxen administration. Plasma naproxen concentrations determined at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the final dose revealed no statistically significant differences between age groups, at either dosage, with respect to total area under the 12-hour time-concentration curve or peak plasma naproxen concentrations. Terminal plasma half-life was longer in the elderly group at each dosage, but these differences are probably not clinically important since the steady state area under the curve was similar in the two age groups. There were no statistically significant changes in serum creatinine levels (monitored as an indicator of kidney function) in either group at either dosage. These results suggest that advanced age per se does not alter naproxen pharmacokinetics in any clinically significant way.