Pharmacokinetics of T-614 after Single Oral Administration in Healthy Korean Volunteers

Dongseong Shin; Bo-Hyung Kim; Jung-Ryul Kim; Kyoung Soo Lim; In-Jin Jang; Sang-Goo Shin; Kyung-Sang Yu

doi:10.12793/jkscpt.2013.21.2.150

Journal List > J Korean Soc Clin Pharmacol Ther > v.21(2) > 1055124

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Shin, Kim, Kim, Lim, Jang, Shin, and Yu: Pharmacokinetics of T-614 after Single Oral Administration in Healthy Korean Volunteers

Original Article

J Korean Soc Clin Pharmacol Ther 2013;21(2):150-158.

Published online: 11 January 2013

DOI: https://doi.org/10.12793/jkscpt.2013.21.2.150

Pharmacokinetics of T-614 after Single Oral Administration in Healthy Korean Volunteers

Dongseong Shin¹, Bo-Hyung Kim², Jung-Ryul Kim³, Kyoung Soo Lim¹, In-Jin Jang¹, Sang-Goo Shin¹, Kyung-Sang Yu¹

¹Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital

²Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital

³Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center

E-mail: ksyu@snu.ac.kr

Received 14 November 201330 December 2013 Accepted 30 December 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Iguratimod is a new type of disease modifying anti-rheumatic drug, which reduced the production of inflammatory cytokines. The purpose of this study was to evaluate pharmacokinetic characteristics and safety profiles of iguratimod after a single oral administration in healthy Korean volunteers.

Methods:

A randomized, double-blind, placebo-controlled, parallel group, single oral dose study was conducted in 24 healthy male volunteers. Three groups of eight subjects each received 25 mg, 50 mg, or 100 mg dosage, respectively. Two subjects in each dose group were administered matching placebo. Plasma concentrations of iguratimod were measured till 72 hours after drug administration. Tolerability was evaluated by monitoring adverse events, clinical laboratory tests, and 12-lead electrocardiograms.

Results:

The mean area under the concentration-time curve from 0 to 72 hours (AUC_last) were 11.9, 25.2, and 51.8 mg × h/L and the maximum plasma concentration (C_max) were 1.15, 2.33, and 4.78 mg/L in 25, 50 and 100 mg dose groups, respectively. All doses of iguratimod were well tolerated without serious adverse events or clinically meaningful changes.

Conclusion:

C_max and AUC_last values of iguratimod proportionally increased with incremental dose. Iguratimod was generally safe and well tolerated.

Keywords: Iguratimod, Pharmacokinetics, Korean

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Figure 1.

Mean plasma concentration-time profiles after oral administration of Iguratimod 25, 50 and 100 mg in healthy Korean subjects. Left panel, semi-log scale; right panel linear scale. Bars represent standard deviations.

Figure 2.

Relationship between pharmacokinetic parameters and dose following single oral Iguratimod doses of 25, 50 and 100 mg. Left panel, log-transformed C_max-dose relationship and right panel, log-transformed AUC_last-dose relationship of Iguratimod.

Figure 3.

Comparison of dose-normalized C_max and AUC_last after single oral administration of Iguratimod 25, 50 and 100 mg. The box edges show lower (25 th) and upper (75 th) quartiles and the line in the middle indicates the median value. Left panel, dose-normalized C_max and right panel, dose-normalized AUC_last.

Table 1.

Demographic characteristics of the 24 healthy volunteers

	Placebo (N= 6)	Iguratimod 25 mg (N=6)	Iguratimod 50 mg (N=6)	Iguratimod 100 mg (N=6)	Total (N=24)	P-value*
Age (years)	25.5 ± 3.4	25.0 ± 3.1	23.0 ± 0.6	23.3 ± 1.2	24.2 ± 2.5	0.189
Weight (kg)	74.3 ± 8.0	67.0 ± 8.3	67.2 ± 6.1	65.7 ± 8.5	68.6 ± 8.0	0.454
Height (cm)	177.2 ± 4.4	174.8 ± 3.4	175.7 ± 4.1	174.0 ± 4.0	175.4 ± 3.9	0.685
BMI (kg/m2)	23.6 ± 1.5	21.9 ± 2.1	21.8 ± 1.8	21.7 ± 2.5	22.5 ± 2.5	0.344

All values are presented as mean ± SD, * Kruskal-Wallis test.

Table 2.

Pharmacokinetic parameters of Iguratimod 25 mg, 50 mg and 100 mg

Dose	Iguratimod 25 mg (N = 6)	Iguratimod 50 mg (N = 6)	Iguratimod 100 mg (N = 6)	P-value**
T_max (h)*	4.05 [3.00 - 4.05]	3.50 [2.00 - 6.00]	4.50 [3.00 - 5.00]	0.709
C_max (mg/L)	1.2 ± 0.2 (20.0)	2.3 ± 0.3 (11.1)	4.8 ± 1.0 (20.7)
C_max/Dose (mg/L/mg)	0.05 ± 0.01 (20.0)	0.05 ± 0.01 (11.1)	0.05 ± 0.01 (20.7)	0.751
AUC_last (mg × h/L)	11.8 ± 2.6 (22.1)	25.2 ± 4.8 (19.1)	51.8 ± 10.3 (19.9)
AUC_last/Dose (mg × h/L/mg)	0.47 ± 0.10 (22.1)	0.50 ± 0.10 (19.1)	0.52 ± 0.10 (19.9)	0.581
AUC_inf (mg × h/L)	11.9 ± 2.6 (22.2)	25.3 ± 4.8 (19.1)	52.0 ± 10.4 (20.0)
AUC_inf/Dose (mg × h/L/mg)	0.48 ± 0.11 (22.2)	0.51 ± 0.10 (19.1)	0.52 ± 0.10 (20.0)	0.581
T_1/2 (h)	9.8 ± 1.4 (14.4)	10.3 ± 2.9 (28.6)	11.6 ± 0.8 (7.1)	0.054
CL/F (L/h)***	2.2 ± 0.4 (20.0)	2.0 ± 0.4 (20.3)	2.0 ± 0.3 (15.7)	0.581
Vd/F (L)	30.6 ± 7.2 (23.6)	29.9 ± 10.2 (34.1)	33.0 ± 5.6 (16.8)	0.198
AUC_%extra*	0.49 [0.22 - 0.97]	0.43 [0.19 - 0.74]	0.47 [0.34 - 0.79]	0.834

*T_max and AUC_%extra are presented as median [minimum - maximum], and other values are presented as mean ± SD (Coefficient of variation, %). **Kruskal-Wallis test. ***CL/F was calculated by Dose/AUC_inf.

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