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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 (AUCτ,ss) and the Cmax at steady state (Cmax,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 AUCτ,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 Cmax,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.
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Figure 2.
Mean (SD) plasma concentration-time profiles of aceclofenac with or without JOINS (upper graph: linear, lower graph: log-linear). Treatment: aceclofenac 100 mg alone (Day 3), aceclofenac 100 mg with JOINS 300 mg (Day 4 and Day 11), τ = 12 h.
Table 1.
Characteristics of the study participants∗
Table 2.
Comparison of the pharmacokinetics of aceclofenac with and without JOINS
| Parameter |
Arithmetic mean ± SD |
Geometric mean ratio (90% CI)a |
|||
|---|---|---|---|---|---|
| Day 3 | Day 4 | Day 11 | Day 4/Day 3 | Day 11/Day 3 | |
| tmax,ss (h)∗ | 2.00 (0.50, 6.00) | 3.00 (0.50, 6.00) | 2.00 (0.50, 6.00) | - | - |
| AUCτ,ss | 22.25 ± 4.55 | 22.01 ± 4.91 | 22.34 ± 4.95 | 0.9858 | 1.0015 |
| τ (h∙μg/mL) | (0.9593–1.0130) | (0.9745–1.0291) | |||
| Cmax,ss | 10.98 ± 3.00 | 10.01 ± 2.48 | 9.90 ± 2.42 | 0.9166 | 0.9093 |
| (μg/mL) | (0.8578–0.9795) | (0.8510–0.9717) | |||
| Cmin,ss (μg/mL) | 0.18 ± 0.20 | 0.13 ± 0.19 | 0.18 ± 0.20 | - | - |
| Cavg,ss (μg/mL) | 1.91 ± 0.37 | 1.89 ± 0.40 | 1.92 ± 0.40 | - | - |
Treatment: aceclofenac 100 mg only (Day 3), aceclofenac 100 mg with JOINS 300 mg (Day 4 and Day 11), τ = 12 h.
∗ The data are presented as the median [min, max]. SD, standard deviation; CI, confidence interval; tmax, time to Cmax; AUCτ, the area under the concentration-time curve during the dosing interval; AUCinf, AUC from dosing time extrapolated to infinity; Cmax, the maximum concentration of drug; Cmin, the minimal drug concentration; Cavg, the average drug concentration during the dosing interval,
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