Comparison of pharmacokinetics and safety of fixed-dose combination of SKI306X and aceclofenac versus separate tablets in healthy subjects

JOINS (SKI306X) is an herbal anti-arthritic medicine that is widely used with aceclofenac for treating osteoarthritis in Korea. A fixed-dose combination (FDC) tablet containing SKI306X and aceclofenac was developed to improve patient compliance. This study aimed to compare the pharmacokinetics (PK) and safety of the FDC tablet with those of co-administered SKI306X and aceclofenac in healthy subjects. In this randomized, open-label, two-way crossover, single-dose study, the FDC tablet (SKI306X 300 mg/aceclofenac 100 mg) (test) was given or co-administration of 300 mg of SKI306X and 100 mg of aceclofenac (reference) was performed followed by a 7-day wash-out period. Blood samples were collected before and after drug administration to evaluate aceclofenac PK parameters, and safety was assessed throughout the study. A total of 54 healthy male subjects were enrolled in and completed the study. T(max) and t(1/2) of aceclofenac of the FDC tablet were similar to those of aceclofenac co-administered with SKI306X (T(max): test 2.96 h and reference 2.14 h; t(1/2): test 3.46 h and reference 4.04 h). The geometric mean ratios (90% confidence intervals) of C(max) and AUC(last) (T/R) were 0.85 (0.81 to 0.91) and 1.03 (1.01 to 1.06) respectively; these results were within the predefined range (0.8 to 1.25). There was only one drug-related adverse event (dizziness) occurred after administration of the FDC tablet; however, it was mild in severity and resolved without any complications. The FDC tablet was well tolerated and exhibited an absorption rate and extent comparable to those of SKI306X and aceclofenac administered simultaneously.

Effects of JOINS® on the pharmacokinetic profiles of aceclofenac in healthy Korean volunteers: an open-label, multiple-dose, one sequence, two-period study

JOINS, an herbal anti-arthritic drug, was developed for the treatment and pain relief of knee osteoarthritis. It was approved for use in Korea by the Ministry of Food and Drug Safety in 2001. The aim of this study was to investigate the effect of JOINS on the pharmacokinetic (PK) profiles of aceclofenac in healthy adults. A PK drug-drug interaction study was conducted in 61 healthy subjects by using an open-label, multiple-dose, one sequence, two-period design. Blood samples were collected for plasma concentrations of aceclofenac during the reference period (aceclofenac 100 mg alone) and interaction period (aceclofenac 100 mg + JOINS 300 mg). The area under the curve within a dosing interval (τ) at steady state (AUC(τ,ss)) and the C(max) at steady state (C(max,ss)) of aceclofenac were analyzed by a non-compartment model using the Phoenix® WinNonlin® software version 6.3 (Pharsight, Mountain View, CA, USA). The 90% CIs of the geometric mean ratios (GMRs) of the AUC(τ,ss) of aceclofenac with JOINS to without JOINS (D4/D3 and D11/D3) were 0.9593–1.0130 and 0.9745–1.0291, respectively, and the corresponding values for the C(max,ss) of aceclofenac with JOINS to without JOINS (D4/D3 and D11/D3) were 0.8578–0.9795 and 0.8510–0.9717. Aceclofenac alone or co-administered with JOINS was safe and well tolerated with no serious adverse drug reactions or significant differences in the severity of adverse events (AEs) between the two treatment groups. We conclude that co-administration of aceclofenac with JOINS does not influence the PK and safety profiles of aceclofenac.