PMID- 22943969
OWN - NLM
STAT- MEDLINE
DCOM- 20130322
LR  - 20131121
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 34
IP  - 10
DP  - 2012 Oct
TI  - 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.
PG  - 2174-83
LID - S0149-2918(12)00489-4 [pii]
LID - 10.1016/j.clinthera.2012.08.008 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier HS Journals, Inc. All rights reserved.
FAU - Marriott, Thomas B
AU  - Marriott TB
AD  - Nuvo Research, Inc, Salt Lake City, Utah, USA. tmarriott@nuvoresearch.com
FAU - Charney, Martha R
AU  - Charney MR
FAU - Stanworth, Stephanie
AU  - Stanworth S
LA  - eng
SI  - ClinicalTrials.gov/NCT01602757
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120901
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anesthetics, Local)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Combinations)
RN  - 0619F35CGV (Tetracaine)
RN  - 98PI200987 (Lidocaine)
SB  - IM
MH  - Administration, Cutaneous
MH  - Adult
MH  - Anesthetics, Local/administration & dosage/adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Delayed-Action Preparations
MH  - Drug Combinations
MH  - Female
MH  - Hot Temperature
MH  - Humans
MH  - Lidocaine/administration & dosage/adverse effects/*pharmacokinetics
MH  - Male
MH  - Tetracaine/administration & dosage/adverse effects/*pharmacokinetics
MH  - Time Factors
MH  - Transdermal Patch
EDAT- 2012/09/05 06:00
MHDA- 2013/03/23 06:00
CRDT- 2012/09/05 06:00
PHST- 2012/05/29 00:00 [received]
PHST- 2012/08/16 00:00 [revised]
PHST- 2012/08/17 00:00 [accepted]
PHST- 2012/09/05 06:00 [entrez]
PHST- 2012/09/05 06:00 [pubmed]
PHST- 2013/03/23 06:00 [medline]
AID - S0149-2918(12)00489-4 [pii]
AID - 10.1016/j.clinthera.2012.08.008 [doi]
PST - ppublish
SO  - Clin Ther. 2012 Oct;34(10):2174-83. doi: 10.1016/j.clinthera.2012.08.008. Epub 
      2012 Sep 1.