Can fractional lasers enhance transdermal absorption of topical lidocaine in an in vivo animal model?
OBJECTIVE
It has been shown in vitro that pretreatment of skin with fractional lasers enhances transdermal delivery of drugs. The aim of this study is to demonstrate in vivo firstly that laser enhances transdermal drug absorption and secondly that this can be manipulated by altering laser settings.


METHODS
Four pigs were used in the IACUC approved animal study. On day 0, 5 g of 4% topical lidocaine was applied under occlusion for 60 minutes to a 400 cm(2) area on the abdomen. Blood was drawn at 0, 60, 90, 120, 180, and 240 minutes. On day 7, the Er:YAG laser was used at 500, 250, 50, and 25 µm ablative depth, respectively, over a 400 cm(2) area on the abdomen. Five grams of 4% topical lidocaine was applied immediately with occlusion for 60 minutes, and then removed. Blood was drawn at 0, 60, 90, 120, 180, and 240 minutes. The serum was extracted and analyzed for lidocaine and its metabolite monoethylglycinexylidide (MEGX).


RESULTS
Serum levels of lidocaine and MEGX were undetectable in untreated skin. Following laser treatment both lidocaine and MEGX were detectable. Peak levels of lidocaine were significantly higher (P = 0.0002) at 250 µm (0.62 mg/L), compared to 500 µm (0.45 mg/L), 50 µm (0.48 mg/L), and 25 µm (0.3 mg/L). Peak levels of MEGX were significantly higher (P ≤ 0.0001) at 250 µm (0.048 mg/L), compared to 500 µm (0.018 mg/L), 50 µm (0.036 mg/L), and 25 µm (0.0144 mg/L).


CONCLUSIONS
This study demonstrates that laser pretreatment significantly increases absorption of topical lidocaine so that it is detectable in the blood and that manipulating laser settings can affect drug absorption. Future work will look at translating this effect into clinical benefit.
Plastic Surgery Department, UT Southwestern Medical Center, Dallas, Texas, USA.
Georgette
G
Oni
Spencer A
SA
Brown
Jeffrey M
JM
Kenkel
D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D053844:Lasers, Solid-State; D008012:Lidocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D012869:Skin Absorption / Q000528:radiation effects*; D013552:Swine
D000779:Anesthetics, Local; D008012:Lidocaine; C001173:monoethylglycinexylidide