Dermatological Agent, Analgesic
Synonyms. Acido Ortóxibenzoico; Acidum Salicylicum; Salizylsäure.
Principal peaks at wavenumbers 758, 1657, 1288, 1210, 1250, 1150 (salicylic acid, KBr disk); 1587, 1724, 1176, 1515, 699, 1041 cm−1 (choline salicylate).
Principal ions at m/z 120, 92, 138, 64, 39, 63, 121, 65; salicyluric acid 121, 120, 69, 92, 195, 39, 93, 45.
Salicylic Acid: Clarke’s Analysis of Drugs and Poisons
Disposition in the Body.
Rapidly absorbed and distributed throughout the body. Metabolised by conjugation with glucuronic acid and glycine to give salicyluric acid, salicyl O-glucuronide, and salicyl ester glucuronide; hydroxylation to gentisic acid, gentisuric acid, and dihydroxy and trihydroxy derivatives also occurs. Excreted in the urine as unchanged drug and metabolites.
Salicylic acid is the major metabolite of aspirin, methyl salicylate, and salsalate.
Following daily oral doses of 9 mg/kg of sodium salicylate to 20 female and 20 male subjects, mean peak plasma concentrations of 57 and 58 mg/L were attained in 0.9 and 0.5 h respectively [S. L. Miaskiewicz et al.,Clin. Pharmacol. Ther.,1982, 31, 30–37].
After daily oral doses of choline salicylate, equivalent to 3.8 g of aspirin, a mean steady–state serum concentration of 166 mg/L was reported [P. D. Hansten and W. L. Hayton,J. Clin. Pharmacol.,1980, 20, 326–331].
The estimated minimum lethal dose is 15 g. Plasma concentrations greater than 300 mg/L are likely to produce toxic effects and concentrations greater than 500 mg/L are associated with moderate to severe intoxication.
In 80 subjects who had ingested an overdose of salicylate either in the form of aspirin tablets (n=42) or as topical medicaments containing methyl salicylate or wintergreen oil (n=38), the plasma salicylate concentrations on admission to hospital were generally higher in the subjects who had ingested aspirin tablets, although the 2 highest readings (4.3 and 3.5 nmol/L) belonged to subjects who had taken topical medicaments [T. Y. Chan,Postgrad. Med. J.,1996, 72, 109–112].
A blood salicylic acid concentration of 6.04 mmol/L was reported in a patient with psoriasis 19 h after he had applied 40% salicylic acid ointment to approximately 41% of his body surface; following haemodialysis, the patient was discharged after 14 days [J. Pec et al.,Cutis,1992, 50, 307–309].
Plasma half–life, dose–dependent (2 to 4 h after salicylate doses of less than 3 g, increasing to about 19 h after large doses).
Volume of distribution.
About 0.1 to 0.2 L/kg (dose–dependent).
In plasma, about 50 to 90% (dose–dependent, about 90% bound at concentrations below 100 mg/L, decreasing to 50% at concentrations above 400 mg/L).
For a review of the pharmacokinetics of salicylates see C. J. Needs and P. M. Brooks,Clin. Pharmacokinet.,1985, 10, 164–177; for a review of drug interactions involving aspirin and salicylic acid, see J. O. Miners,Clin. Pharmacokinet.,1989, 17, 327–344; for a brief review of ototoxicity associated with salicylates, see J. A. Brien,Drug Saf.,1993, 9, 143–148.
Salicylic acid is applied topically in concentrations usually ranging from 1 to about 6% as a keratolytic; up to 60% is used as a caustic in preparations for the removal of warts. Sodium salicylate is given by mouth in doses of up to 5.4 g daily.