Oxaprozin pharmacokinetics in the elderly

Abstract

A series of 42 healthy male and female volunteers aged 21 to 89 years received a single 1200 mg oral dose of oxaprozin. Kinetics were determined from multiple plasma oxaprozin concentrations measured by h.p.l.c. during 14 days after the dose. Peak plasma oxaprozin concentrations were reached between 3 and 6 h after dosage the majority of subjects, probably reflecting slow absorption from the gastrointestinal tract. Elimination also was slow with a mean half-life of 59 h (range 36 to 92 h). Owing in part to extensive protein binding (mean free fraction 0.0023%), oxaprozin distribution was limited, with apparent volume of distribution averaging 0.25 l/kg. Apparent volume of distribution declined with increasing age, probably reflecting the reduction in lean mass relative to total weight that occurs in the elderly. Total apparent oxaprozin clearance declined with age in men (r = -0.58, P less than 0.01), but was not significantly related to age in women (r = -0.25, NS). This is consistent with the previously described gender-specific reduction in hepatic oxidizing capacity association with increasing age. Thus oxaprozin is a slowly eliminated nonsteroidal anti-inflammatory agent that should be suitable for once daily or every other day administration.