Nonlinear Pharmacokinetics of Topical Flurbiprofen Gel in a Phase I Study Among Chinese Healthy Adults.

Autor: Xiao W; Division of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, No. 172 Tongzipo Road, Changsha, 410013, China.; Hunan Jiudian Pharmaceutical Co., Ltd., Changsha, 410009, China., Zhu Z; Hunan Jiudian Pharmaceutical Co., Ltd., Changsha, 410009, China., Xie F; Division of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, No. 172 Tongzipo Road, Changsha, 410013, China., Liu F; Division of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, No. 172 Tongzipo Road, Changsha, 410013, China. feiyan.liu@csu.edu.cn., Cheng Z; Division of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, No. 172 Tongzipo Road, Changsha, 410013, China. chengzn@csu.edu.cn.
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2024 May; Vol. 41 (5), pp. 911-920. Date of Electronic Publication: 2024 Mar 20.
DOI: 10.1007/s11095-024-03692-4
Abstrakt: Introduction: PDX-02 (Flurbiprofen sodium) is a topical nonsteroidal anti-inflammatory drug in gel formulation for local analgesia and anti-inflammation. A Phase I clinical trial was conducted to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of PDX-02 gel in Chinese healthy adults.
Methods: The trial comprised three parts: (1) a single-dose ascending study with three dose levels (0.5%, 1% to 2% PDX-02 gel) applied on a 136 cm 2 skin area; (2) a multiple-dose study with either 1% or 2% PDX-02 gel applied on a 136 cm 2 skin area for 7 consecutive days; and (3) a high dose group with 2% PDX-02 gel on an 816 cm 2 skin area and a frequent multiple dose group with 2% PDX-02 gel on a 272 cm 2 skin area four times a day for 7 consecutive days. The safety, tolerability and pharmacokinetics of the PDX-02 gel were evaluated in each part.
Results: A total of sixty participants completed the trial, with all adverse events recovered and all positive skin reaction being transient and recovered. The overall absorption of topical PDX-02 gel was slow with a mean peak time exceeding 9 h. The elimination rate remained consistent between dose groups. A less-than-dose-proportional nonlinear pharmacokinetics relationship was observed within the studied dose range, and this is likely due to the autoinduction of skin first-pass metabolism.
Conclusion: The topical PDX-02 gel showed favorable safety and tolerability in both single and multiple dosing studies, with a less-than-dose-proportional nonlinear pharmacokinetics observed.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: