A Randomized, Crossover, Pharmacokinetic and Adhesion Performance Study of a Lidocaine Topical System 1.8% During Physical Activity and Heat Treatment in Healthy Subjects
Received 21 November 2019
Accepted for publication 7 May 2020
Published 10 June 2020 Volume 2020:13 Pages 1359—1367
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 5
Editor who approved publication: Dr E Alfonso Romero-Sandoval
Jeffrey Fudin,1– 4 Erica L Wegrzyn,1– 3 Emileigh Greuber,5 Kip Vought,5 Kalpana Patel,5 Sri Nalamachu6
1Samuel Stratton Department of Veterans Affairs Medical Center, Albany, NY, USA; 2Albany College of Pharmacy & Health Sciences, Albany, NY, USA; 3Western New England University College of Pharmacy, Springfield, MA, USA; 4Remitigate, LLC, Delmar, NY, USA; 5Scilex Pharmaceuticals Inc., Mountain View, CA, USA; 6Mid America PolyClinic, Overland Park, KS, USA
Correspondence: Jeffrey Fudin
Remitigate, LLC, Delmar, NY 12054, USA
Tel +1 518-772-4100
Fax +1 518-734-0288
Purpose: This study compares the pharmacokinetic (PK) profile, adhesion, and safety of lidocaine topical system 1.8%, a novel lidocaine topical system approved to treat postherpetic neuralgia, under conditions of heat and exercise vs normal conditions.
Materials and Methods: This open-label, 3-period, 3-treatment crossover study randomized 12 healthy adults to receive three lidocaine topical systems 1.8% during each of three treatment periods, with 7-day washouts between treatments. The product was applied to the mid-lower back and was removed after 12 hours. During Treatment A, subjects exercised on a bicycle for 30 minutes at 0, 2.5, 5.5, and 8.5 hours. During Treatment B, heat (temperature set at 36.7– 40.3°C) was applied at 0 and 8.5 hours. Treatment C was normal conditions. The PK profile of each subject under exercise and heat conditions was compared to normal conditions. Skin irritation, adhesion, and adverse events were assessed.
Results: Twelve subjects completed the study. Exposure to external heat resulted in increased peak plasma concentration of lidocaine with a mean Cmax of 160.3± 100.1 ng/mL vs 97.6± 36.9 ng/mL under normal conditions, with no effect on the extent of exposure (AUC). Concentrations returned to normal within 4 hours after the heat was removed. No clinically relevant differences in absorption were observed under exercise conditions with a mean Cmax of 90.5± 25.4 ng/mL and no effect on the extent (AUC) of lidocaine exposure was observed relative to normal conditions. No systems detached during the study. Adverse events were mild, with none leading to discontinuation.
Conclusion: Transient heat exposure resulted in increased lidocaine plasma concentrations compared to normal conditions, whereas exercise had no effect. The effects of heat appear to be immediate, reversible, and below systemic therapeutic threshold in antiarrhythmic treatment (1000– 1500 ng/mL), and well below the safe systemic threshold of 5000 ng/mL. Lidocaine topical system 1.8% remained adhered to the skin and was well tolerated under all conditions. ClinicalTrials.gov: NCT04150536.
Keywords: herpes zoster, shingles, neuropathic pain, dermal
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