Jung Woohyung, Seok Su Hyun, Shin Soyoung, Ryu Sung Ha, Kim Kyu-Bong, Shin Beom Soo, Kim Tae Hwan
College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Gyeongbuk, Korea.
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Gyeonggi, Korea.
Toxics. 2022 Nov 7;10(11):672. doi: 10.3390/toxics10110672.
The aim of this study was to evaluate in vitro skin permeation and deposition, in vivo toxicokinetics, percutaneous absorption and tissue distribution of benzophenone-3 (BP-3) in rats. Four transdermal formulations containing BP-3 were prepared and evaluated for in vitro skin permeation and deposition of BP-3 using Franz diffusion cells. A gel formulation was used in subsequent in vivo percutaneous absorption due to its high in vitro skin permeation and deposition. Compared to intravenous (i.v.) injection, the prolonged terminal t (3.1 ± 1.6 h for i.v. injection and 18.3 ± 5.8 h for topical application) was observed indicating occurrence of flip-flop kinetics after topical application. The bioavailability of BP-3 after topical application was 6.9 ± 1.8%. The tissue-to-plasma partition coefficient (kp) for testis, considered a toxic target for BP-3, was less than 1.. Overall, findings of this study may be useful for risk assessment of BP-3.
本研究旨在评估二苯甲酮 - 3（BP - 3）在大鼠体内的体外皮肤渗透与沉积、体内毒代动力学、经皮吸收及组织分布情况。制备了四种含BP - 3的透皮制剂，并使用Franz扩散池评估BP - 3的体外皮肤渗透与沉积。由于其体外皮肤高渗透与沉积特性，一种凝胶制剂被用于后续的体内经皮吸收研究。与静脉注射相比，观察到终末半衰期延长（静脉注射为3.1±1.6小时，局部应用为18.3±5.8小时），表明局部应用后出现了翻转动力学。局部应用后BP - 3的生物利用度为6.9±1.8%。睾丸被认为是BP - 3的毒性靶点，其组织 - 血浆分配系数（kp）小于1。总体而言，本研究结果可能有助于BP - 3的风险评估。
