Biorelevant In Vitro Skin Permeation Testing and In Vivo Pharmacokinetic Characterization of Lidocaine from a Nonaqueous Drug-in-Matrix Topical System.

"Declarations Conflict of InterestEmileigh Greuber reports employment with Scilex Pharmaceuticals, Inc., during the conduct of the study and is currently with Regulatory and Strategic Development, Clinipace, Inc., Morrisville, NC, USA. Kip Vought reports employment with Scilex Pharmaceuticals, Inc., during the conduct of the study. Kalpana Patel reports employment with Scilex Pharmaceuticals, Inc., during the conduct of the study and outside the submitted work. Hiroaki Suzuki, Kazuhiro Usuda, and Akira Shiramizu report nothing to disclose. Luana Pesco Koplowitz reports receiving consultancy fees from Scilex Pharmaceuticals, Inc., during the conduct of the study. Barry Koplowitz reports receiving consultancy fees from Scilex Pharmaceuticals, Inc., during the conduct of the study. Howard I. Maibach reports receiving consultancy fees from Scilex Pharmaceuticals, Inc., as a Principal Scientist. Dmitri Lissin reports employment with Scilex Pharmaceuticals, Inc., during the conduct of the study and outside the submitted work. This article is the sole work of the authors; stated opinions or assertions do not reflect the opinions of employers or employee affiliates listed. Conflict of Interest Emileigh Greuber reports employment with Scilex Pharmaceuticals, Inc., during the conduct of the study and is currently with Regulatory and Strategic Development, Clinipace, Inc., Morrisville, NC, USA. Kip Vought reports employment with Scilex Pharmaceuticals, Inc., during the conduct of the study. Kalpana Patel reports employment with Scilex Pharmaceuticals, Inc., during the conduct of the study and outside the submitted work. Hiroaki Suzuki, Kazuhiro Usuda, and Akira Shiramizu report nothing to disclose. Luana Pesco Koplowitz reports receiving consultancy fees from Scilex Pharmaceuticals, Inc., during the conduct of the study. Barry Koplowitz reports receiving consultancy fees from Scilex Pharmaceuticals, Inc., during the conduct of the study. Howard I. Maibach reports receiving consultancy fees from Scilex Pharmaceuticals, Inc., as a Principal Scientist. Dmitri Lissin reports employment with Scilex Pharmaceuticals, Inc., during the conduct of the study and outside the submitted work. This article is the sole work of the authors; stated opinions or assertions do not reflect the opinions of employers or employee affiliates listed."

"Funding This research was funded by Scilex Pharmaceuticals Inc."

"Fifteen healthy, nonsmoking, adult male and female volunteers were enrolled. The study protocol was approved by IntegReview Institutional Review Board (Austin, TX, USA) and conducted in accordance with Good Clinical Practice and the Declaration of Helsinki. Eligible subjects were men and women 18–60 years of age with BMI between 18 and 32.5 kg/m2, nonsmokers, and generally healthy as documented by 12-lead electrocardiogram and clinical laboratory assessments. Female subjects could not be pregnant or lactating, and those of childbearing potential were instructed to practice medically acceptable contraception throughout the study. Exclusion criteria included evidence of allergy or known hypersensitivity to lidocaine, local anesthetics of the amide type, or any of the components of the lidocaine topical system formulation. Subjects were excluded if they had any major illness in the last 3 months or any significant chronic medical illness, history of addiction, and abuse or misuse of any drug or had any skin condition that may affect the application of the study product. The study was conducted at Axis Clinicals (Dilworth, MN, USA) and is registered with ClinicalTrials.gov, NCT04819581."