Percutaneous absorption and metabolism of lonapalene in psoriatic skin.
The percutaneous absorption and metabolism of lonapalene (6-chloro-2,3-dimethoxynaphthalene-1,4-diol-diacetate; RS-43179), a topically effective 5-lipoxygenase inhibitor, has been measured in six subjects with stable plaque-type psoriasis of the lower extremities. Lonapalene readily penetrates psoriatic skin, is rapidly and completely metabolized, and is almost entirely excreted in the urine. Unexpectedly we observed a trend for thigh (T) plaque skin to be more permeable than lower leg (LL) plaque skin as measured by total absorption (T, 44.8 +/- 13.4%; LL, 24.9 +/- 12.6% applied dose excreted), peak plasma levels (T, 209 +/- 107; LL, 146 +/- 81 ng Eq/ml), and peak rate of urinary excretion (T, 591.7 +/- 112.2; LL, 318.4 +/- 143.9 micrograms Eq/hr). There were also differences in the metabolic profiles between the two sites as measured by the quantity and proportion of dealkylated and conjugated products excreted in the urine.
Lehman
P A
PA
Division of Dermatology, School of Medicine, University of Washington, Seattle 98115.
Tomlinson
R V
RV
Johnson
J I
JI
Olerud
J E
JE
Akers
W A
WA
Franz
T J
TJ
D000279:Administration, Cutaneous; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D009281:Naphthalenes / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D012869:Skin Absorption
D016859:Lipoxygenase Inhibitors; D009281:Naphthalenes; C045954:RS 43179