Effects of application durations and heat on the pharmacokinetic properties of drug delivered by a lidocaine/tetracaine patch: a randomized, open-label, controlled study in healthy volunteers.

BACKGROUND: The lidocaine/tetracaine heated patch is typically applied to the skin for 20 to 30 minutes to provide local dermal analgesia prior to venous access or minor dermatologic procedures. The potential exists for the use of multiple heated patches for longer application times, but the pharmacokinetic properties and tolerability of these multiple and/or longer applications have not been assessed. OBJECTIVE: The aim of this study was to assess the effects of heat and application time on the pharmacokinetic properties and tolerability of the patch after the application of 4 lidocaine/tetracaine (70/70 mg) heated patches applied at the same time in healthy volunteers for up to 12 hours. METHODS: In this randomized, open-labeled, controlled study, healthy subjects underwent 4 treatment periods (2-, 4-, or 12-hour application of 4 heated patches, or 4-hour application of 4 unheated patches), each separated by a 1-week washout period. RESULTS: Twelve subjects were enrolled (8 women, 4 men; mean age, 31.8 years; mean body mass index, 24.1 kg/m(2)). No tetracaine was detected in the plasma of any subject. Plasma concentrations of lidocaine increased rapidly during the first 2 hours of application in each heated-patch group, and with mean (SD) C(max) values of 18.2 (5.1), 25.7 (5.9), and 30.3 (8.1) ng/mL in the 2-, 4-, and 12-hour groups, respectively. Estimates of application time-normalized AUC(0-t) were not significantly different between the 2- and 4-hour applications of the heated patches, but were 25% lower during the 12-hour application time, suggesting continued but diminished drug delivery between 4 and 12 hours. Compared with subjects who received the unheated patch, those who received the heated patch had plasma lidocaine concentrations 5- and 3-fold higher after 30 and 60 minutes, respectively. Fifteen mild to moderate adverse events (AEs) were reported in 7 subjects, and none of the subjects discontinued the study due to treatment-related AEs. CONCLUSION: The heated patch continuously delivered drug for up to 12 hours and was generally well tolerated in these healthy subjects. ClinicalTrials.gov identifier: NCT01602757.