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

Abstract

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.

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

“…[1,[7][8][9] In addition, SKI306X did not influence the PK and safety of aceclofenac when it was concomitantly administered. [7] Based on these facts, an FDC tablet containing aceclofenac and SKI306X was developed. The aim of the study was to evaluate the PK of aceclofenac and the safety of the FDC tablet compared to those of the co-administration of aceclofenac and SKI306X in healthy adults.…”

“…[1] SKI306X has been widely used in combination with aceclofenac in Korea for pain control in OA. [6] Even though the active moiety of SKI306X and its metabolites has not been established and its pharmacokinetic (PK) characteristics are unknown, [7] SKI306X has demonstrated efficacy in pain control and protective effects in articular cartilage through its anti-inflammatory and immunomodulatory actions without notable side effects. [1,[7][8][9] In addition, SKI306X did not influence the PK and safety of aceclofenac when it was concomitantly administered.…”

“…[18] In addition, SKI306X did not influence the PK and safety of aceclofenac in co-administration. [7] The FDC tablet containing aceclofenac and SKI306X was developed to improve patient adherence based on the results of previous PK interaction study. [7] In this study, the PK results demonstrated that the FDC tablet was pharmacokinetically bioequivalent to the co-administration of aceclofenac and SKI306X.…”

“…[7] The FDC tablet containing aceclofenac and SKI306X was developed to improve patient adherence based on the results of previous PK interaction study. [7] In this study, the PK results demonstrated that the FDC tablet was pharmacokinetically bioequivalent to the co-administration of aceclofenac and SKI306X. The 90% confidence intervals of the geometric mean ratios of C max and AUC last for aceclofenac were within the predetermined range of 0.80-1.25, which is generally accepted as bioequivalent.…”