108 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 18 •12 j• I I IO%METH. SAL IN ETHER • _ _ I -I / // •--N-BUTYL + E - -II / • /.---ISO AMYL E - II / • •-- •PHENYL + ••=-• I i•BENZYL + E o (M•N.) TIME (HOURS) Fig. 18.--Percutaneous absorption of different salicylate esters in ether (s:dicyl- ate ester as salicylic acid). salicylic acid were compared because these vehicles quickly evaporate eliminating any "vehicle effect." Comparisons of the percutaneous absorp- tion of different salicylate derivatives (in 10 per cent solutions) by the plas- ma, salicylic acid and ester salicylate levels are presented in Figs. 17 and 18, respectively. Ethyl and methyl salicylates produced the highest plasma salicylic acid levels (significant). Methyl salicylate is significantly better • I I I _• HYL SALICYL n 6 - tic 4 - - I • 0 •' , I i I I5 30 o (MIN.) I 2 3 TIME (HOURS) Fig. 19.--Percutaneous absorption of 10% ethyl salicylate and 10% ethyl aspirin in ether.

THE PERCUTANEOUS ABSORPTION OF SALICYLATES 109 • 40 • zo I I I /// ///' /....,,,"•/4 ABRADED ii // • I// // //•/// ,. ' - // /" I I I 0 [ 2 • TIME (HOURS) Fig. 20.--The effect of abrading different amounts of the absorption area on percutaneous absorption of 10% methyl salicylate in mineral oil. absorbed than ethyl salicylate. Isopropyl salicylate is significantly better than all the remaining ones except for N-butyl and phenyl salicylates and after one hour salicyl phosphate, sodium salicylate, morpholine salicylate and diethylamine salicylate produced significantly lower plasma salicylic acid levels than all the others. The plasma ester curves are slightly dif- ferent in appearance perhaps due to differences in distribution, excretion or hydrolysis rate. I I I LIGHT MINERAL OIL METHYL NICOTINATE AND _ -- LIGHT MIN. OIL //.•'/ METHYL NICOTI NATE / /•" POLYETHYLENE _ r /.• -GLYCOL MIX / 'OLYETHYLE.E L"•.,.•*:"-•==":ø-I I I GLYCOL MIX I 2 3 TIME (HOURS) Fig. ?-].--Effect ooe 0.9_.5% methyl nicotinate on percutaneous absorption ooe ]0% methyl salicylate in mineral oil and polyethylene glycol.