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Choi, Kim, Chung, Cho, Yu, Jang, and Lim: A Randomized, Open Label, 2-Way Crossover Study to Assess the Pharmacokinetic Characteristics and Skin Irritation of Murupe® Patch Compared with Trast® Patch in Healthy Volunteers
Original Article

J Korean Soc Clin Pharmacol Ther 2013;21(1):41-51.

Published online: 11 January 2013

DOI: https://doi.org/10.12793/jkscpt.2013.21.1.41

A Randomized, Open Label, 2-Way Crossover Study to Assess the Pharmacokinetic Characteristics and Skin Irritation of Murupe® Patch Compared with Trast® Patch in Healthy Volunteers

Yoon Jung Choi1, Young Mi Kim2, Jae-Yong Chung1, Joo-Youn Cho1, Kyung-Sang Yu1, In-Jin Jang1, Kyoung Soo Lim1

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

2College of Pharmacy, Hanyang University, Ansan-Si, Gyeonggi-Do, Republic of Korea

E-mail: kslim96@snu.ac.kr

Received 19 June 201324 June 2013       Accepted 26 June 2013

Copyright © 2013 Korean Society for Clinical Pharmacology and Therapeutics

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:

A piroxicam patch has been widely used to treat musculoskeletal pain. The aim of this study was to assess the pharmacokinetic (PK) characteristics and skin irritation of Murupe® patch (piroxicam 96 mg) compared with Trast® patch (piroxicam 96 mg) in healthy volunteers.

Methods:

A randomized, open-label, 2-way crossover study was conducted in 12 healthy Korean male subjects. They were allocated to one of the two treatment sequences of RT and TR (R, reference drug, Trast® patch; T, test drug, Murupe® patch). Each patch was applied to the subject once during 48 hours. Serial blood samples were collected up to 72 hours after removing the patch and plasma concentrations were determined by high performance liquid chromatography. Safety was monitored and the skin irritation potential was assessed.

Results:

The plasma concentration - time profile during 48 hours showed an exponential increase in both of two patch products. Mean Cmax and AUClast values were not statistically different between two patch groups. Mean AUC[0-48h] was lower in Murupe® patch group than that in Trast® patch group; 806.4 and 1196.5 ng·h/mL However, the mean AUC[48-120h] value tended to be higher in Murupe® patch group, implying more delayed excretion than in Trast® patch group; 2724.7 ng·h/mL and 1989.2 ng·h/mL. The overall results of skin irritation potential test showed no clinically significant differences between two patch groups.

Conclusion:

Mean Cmax and AUClast values in Murupe® patch group were comparable to those in Trast® patch group. Murupe® patch was safe and well tolerated in healthy male subjects.

Keywords: Piroxicam patch, Pharmacokinetics, Skin irritation

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Figure 1.
Mean plasma piroxicam concentration-time profile by treatment group. Bars represent standard deviations (Left: linear scale, right: log-linear scale. ∘ : Murupe® patch. • : Trast® patch).
jkscpt-21-41f1.tif
Table 1.
Demographic data of subjects
Treatment sequences
 Total (n=12) P-value†
RT* (n=6) TR* (n=6)
Age (yrs) 24.7 ± 4.6 26.3 ± 6.7 25.5 ± 5.6 0.628
Height (cm) 175.9 ± 4.0 175.7 ± 9.2 175.8 ± 6.8 0.953
Weight (kg) 73.1 ± 7.3 65.3 ± 9.9 69.2 ± 9.2 0.155

Data are presented as mean ± standard deviation. * R: Reference drug (Trast® patch), T: Test drug (Murupe® patch). † Wilcoxon rank sum test.

Table 2.
Adverse event profile
Period Treatment sequence
 Total†
RT TR*
Number of subjects
Period 1 2 / 6 1 / 6 (1 / 7)‡ 3 / 12 (3 / 13)‡
Period 2 2 / 6 1 / 6 3 / 12
Total 2 / 6 2 / 6 (2 / 7)‡
Number of adverse events
Period 1 2 1 (1) 3 (3)
Period 2 2 1 3
Total 4 2 (2)

* T: Test drug (Murupe® patch), R: Reference drug (Trast® patch). † Chi-square test. ‡ These data include adverse events occurred in those who withdrew after period 1.

Table 3.
Evaluation of skin irritation test taken from two sides of the attachment sites
Treatment
 P-value§
Murupe® patch Trast® patch
PSI*
Lateral 0.44 ± 0.36 0.04 ± 0.14 0.0012
Middle 0.44 ± 0.36 0.04 ± 0.14 0.0012
Medial Control
 0 ± 0
 0 ± 0
 1.0
LDF†
Lateral 6.23 ± 7.92 2.18 ± 2.04 0.2852
Middle 7.43 ± 12.17 1.60 ± 3.64 0.1123
Medial Control
 0.62 ± 3.09
 0.48 ± 4.23
 0.7074
TEWL‡
Lateral 3.03 ± 2.20 0.90 ± 3.82 0.0303
Medial 2.54 ± 4.07 2.54 ± 4.07 0.4529
Medial Control 1.83 ± 3.41 0.24 ± 1.40 0.1652

Data are presented as mean ± standard deviation. * PSI (primary skin irritation). † LDF (laser doppler blood flowcytometry). ‡ TEWL (transepidermal water loss measurement). § Wilcoxon rank sum test.

Table 4.
Summary of pharmacokinetic parameters
Parameter Murupe® patch Trast® patch Ratio‡ (90 % CI)
Cmax 45.5 ± 37.9* 42.8 ± 20.6 0.90
(ng/mL) 3.54 ± 0.74† 3.65 ± 0.48 (0.62 - 1.30)
AUC[0-48h] 806.4 ± 785.3 1196.5 ± 616.0 0.55
(ng·h/mL) 6.37 ± 0.79 6.97 ± 0.51 (0.37 - 0.81)
AUC[48-120h] 2724.7 ± 2319.0 1989.2 ± 862.3 1.13
(ng·h/mL) 7.63 ± 0.75 7.51 ± 0.45 (0.78 - 1.64)
AUClast 3531.6 ± 3085.0 3186.6 ± 1448.7 0.91
(ng·h/mL) 7.88 ± 0.76 7.97 ± 0.47 (0.63 - 1.33)

* Mean ± SD. † Log-transformed mean ± SD. ‡ These data are reported on the exponential of the means of log-transformed values (CI = confidence interval).

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