Bioequivalence and pharmacokinetic evaluation of two branded formulations of aceclofenac 100 mg: a single-dose, randomized, open-label, two-period crossover comparison in healthy Korean adult volunteers.
BACKGROUND
Aceclofenac is a phenylacetic acid derivative with analgesic and anti-inflammatory properties and an improved gastrointestinal tolerance compared with other NSAIDs, such as diclofenac.


OBJECTIVE
This study was conducted to compare the bioavailability of 2 branded formulations of aceclofenac 100 mg (test and reference) marketed in Korea.


METHODS
This single-dose, randomized, open-label, 2-period crossover study in healthy Korean adult volunteers was conducted at Hanyang University Medical Center (Seoul, Republic of Korea). Subjects received 1 tablet of each aceclofenac 100-mg formulation. Study drugs were administered with 240 mL of water after a 10-hour overnight fast on each of 2 treatment days separated by a 1-week washout period. After study drug administration, serial blood samples were collected over a period of 12 hours. Plasma was analyzed for aceclofenac concentration using a validated high-performance liquid chromatography method with visible detection in the range of 0.1 to 20 microg/mL, with a lower limit of quantitation of 0.1 microg/mL. Several pharmacokinetic (PK) parameters, including C(max), T(max), t(1/2), AUC(0-t), AUC(0-infinity), and k(e), were determined from the plasma concentrations of the 2 aceclofenac formulations. C(max), AUC(0-t), and AUC(0-infinity) were used to test for bioequivalence after log-transformation of plasma data. The predetermined, regulatory range of 90% CI for bioequivalence was 0.80 to 1.25.


RESULTS
A total of 24 subjects were enrolled (20 men, 4 women; mean [SD] age, 23.5 [1.4] years; mean [SD] weight, 68.1 [11.5] kg). No significant differences were found based on analysis of variance, with mean values and 90% CIs of test/reference ratios for these parameters as follows: C(max), 10.57 versus 9.79 microg/mL (0.961-1.225); AUC(0-t), 19.95 versus 19.93 microg x h/mL (0.937-1.037); and AUC(0-infinity), 20.75 versus 20.48 microg x h/mL (0.949-1.049).


CONCLUSIONS
In these healthy Korean volunteers, results from the PK analysis suggested that the test and reference formulations of aceclofenac 100-mg tablets were bioequivalent, based on the regulatory definition.
Rhim
Si-Youn
SY
Division of Pediatric Surgery, Department of Surgery, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Park
Jin-Hee
JH
Park
Yoo-Sin
YS
Lee
Min-Ho
MH
Shaw
Leslie M
LM
Kang
Ju-Seop
JS
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007723:Korea; D008297:Male; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy; D010146:Pain / Q000097:blood / Q000188:drug therapy; D012016:Reference Values; D013810:Therapeutic Equivalency
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; C056498:aceclofenac