Nabumetone kinetics in the young and elderly.
Nabumetone, a nonsteroidal anti-inflammatory drug of the naphthylalkanone class, was studied in an open-label fashion to compare the relative single-dose and steady-state kinetics in young healthy male volunteers and in elderly patients with degenerative joint disease. Seventeen healthy male volunteers 21 to 30 years of age and 17 patients 60 to 75 years of age were studied. After a single oral dose of 1,000 mg nabumetone, blood and urine samples were collected over a five-day period. Plasma was assayed for nabumetone and the active metabolite, 6-methoxynaphthylacetic acid, and the urine was assayed for five metabolites. Following this phase, they received daily oral doses of 1,000 mg nabumetone for 14 days. After the final dose, blood and urine samples were again collected for five days for the same assays. These data were fitted to a single compartment model and the derived data are as follows: mean maximal plasma concentration, maximal time concentration, area under the plasma-time curve, elimination rate constant, and elimination half-life in the young group after single dose were 22.9, 8.4, 838, 0.032, and 21.2, respectively, whereas on steady-state, values were 33.6, 4.1, 666, 0.031, and 22.1, respectively. In the elderly group after single dose, these values were 30.2, 10.8, 1,538, 0.024, and 29.2, whereas on steady-state, they were 50.0, 7.2, 1,092, 0.027, and 25.6. The accumulation ratio was 1.6 in the young and 1.8 in the elderly. Side effects in the young were mild and consistent of headaches, epigastric discomfort, nausea, and vomiting, whereas in the elderly they consisted mainly of headaches. No significant changes in complete blood cell count, blood chemistries, or urinalysis were noted. We concluded from these data that the drug does not accumulate if given every 24 hours; therefore, a single daily dose should provide sufficient therapy and that due to a difference in elimination, elderly patients may require a lower dose.
McMahon
F G
FG
Clinical Research Center, Tulane University Medical Center, New Orleans, Louisiana.
Vargas
R
R
Ryan
J R
JR
Fitts
D A
DA
D000328:Adult; D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002074:Butanones / Q000493:pharmacokinetics*; D006801:Humans; D000077430:Nabumetone; D010003:Osteoarthritis / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D000077430:Nabumetone