In vitro cutaneous disposition of a topical diclofenac lotion in human skin: effect of a multi-dose regimen.
OBJECTIVE
This study determines comparative bioavailability of diclofenac sodium lotion compared to an aqueous solution after topical application to viable human skin in vitro. In addition, the difference between a single dose and multiple doses (8 times) was also determined.


METHODS
An in vitro flow-through diffusion cell system was employed, using radiolabelled diclofenac sodium.


RESULTS
Multiple doses of lotion (2 microl/cm2 and 5 microl/cm2) delivered a total of 40.1 +/- 17.6 microg and 85.6 micro 41.4 microg diclofenac, respectively, at 48 h, compared to only 9.4 +/- 2.9 microg and 35.7 +/- 19.0 microg absorbed after topical application of diclofenac as an aqueous solution (P < 0.05). A single dose study showed no statistical difference between diclofenac delivered in lotion or an aqueous solution. Over 48 h the total absorption from lotion was 10.2 +/- 6.7 microg and 26.2 +/- 17.6 microg (2 microl/cm2 and 5 microl/cm2, respectively), compared to 8.3 +/- 1.5 microg and 12.5 +/- 5.7 microg from an aqueous solution. Both single doses of lotion and aqueous diclofenac showed decreased diclofenac absorption into the receptor fluid between 12 and 24 h. However, when applied multiple times, absorption from lotion was continually increasing up to 48 h. The total dose accountability ranged from 76.8 +/- 8.2% to 110.6 +/- 15. 1% of the applied dose.


CONCLUSIONS
Diclofenac lotion exhibited enhanced diclofenac percutaneous absorption rate through human skin (mass, flux and partition coefficient) when applied a multiple number of times and this enhanced absorption was maintained over 48 h. This suggests that a constituent of the lotion (DMSO) will enhance human skin absorption of diclofenac when used in a multi-dose regimen, but not after a single dose.
Hewitt
P G
PG
Department of Dermatology, University of California, San Francisco, Surge Laboratory, 94143, USA.
Poblete
N
N
Wester
R C
RC
Maibach
H I
HI
Shainhouse
J Z
JZ
D000287:Administration, Topical; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D019344:Lactic Acid / Q000096:biosynthesis; D009824:Ointments; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000502:physiology*; D012996:Solutions; D014867:Water
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009824:Ointments; D012996:Solutions; D014867:Water; D004008:Diclofenac; D019344:Lactic Acid