Bioequivalence study of nabumetone: tablet versus suspension.
The orally administered tablet and suspension of the analgesic drug nabumetone (Relafen), a novel naphthylalkanone, were tested for bioequivalence. Nabumetone is rapidly metabolized to an active metabolite, 6-methoxy-2-naphthylacetic acid (BRL 10720). The pharmacokinetics of the metabolite were studied in 24 healthy adult male volunteers. Each received a 1-g dose of the nabumetone formulations in a balanced, randomized, two-way crossover investigation. Serum metabolite concentrations were determined over a 120-hour interval by high-performance liquid chromatography. The values of the pharmacokinetic parameters computed for tablet and suspension are presented in that order: area under the curve = 1,269:1,338 mg.hour/ml; absorption half-life = 1.04:0.83 hour; elimination half-life = 27.16:25.15 hours; lag time = 0.19:0.07 hour; peak concentration = 27.56:31.91 micrograms/ml, and time to peak concentration = 4.99:4.17 hours. The mean concentration of BRL 10720 was found to be higher during the first eight hours for the suspension than for the tablet. Using criteria for statistical significance, the values for peak concentration, time to peak concentration, elimination half-life, and lag time were found significant (p less than 0.05). These results may well be reflecting the increased absorption characteristics of the suspension due to the pharmaceutical characteristics of the preparation. The formulations were found to be bioequivalent when compared on the premise that no significant difference was detected when area under the curve and all other parameters were compared, based upon the 75/75 rule analysis.
Daigneault
E A
EA
Department of Pharmacology, East Tennessee State University, College of Medicine, Johnson City 37614.
Ferslew
K E
KE
Stanton
P
P
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002074:Butanones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D000077430:Nabumetone; D009280:Naphthaleneacetic Acids / Q000493:pharmacokinetics; D013535:Suspensions; D013607:Tablets; D013810:Therapeutic Equivalency
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D009280:Naphthaleneacetic Acids; D013535:Suspensions; D013607:Tablets; C044612:6-methoxy-2-naphthylacetic acid; D000077430:Nabumetone