Salicylic acid pharmacokinetics

Determination in Biological Fluids and Tissues All the advances in pharmacokinetics and drug metabolism described in Sections 7 and 8 would not have been possible without the availability of the proper analytical methods. The following is a tabulation of publications in this field, most of which have already been discussed in Section 5. It should be mentioned that a few publications talk about aspirin blood levels, but really mean salicylate levels. The following tabulation covers only those papers where aspirin was differentiated from other salicylates by chromatography or other means. It seems that the "workhorse" for serum salicylate levels is still the colorimetric (ferric-nitrate) method of Brodie, Udenfriend and Coburn153 published in 1944, or modifications thereof. Simplified versions (cf. 206) may lead to erroneous results under certain conditions.207 The method is also applicable for urinary metabolites after proper hydrolysis (cf. 208). For other methods restricted to salicylic acid, see Section 5.61. 

Lau, A.H. Chang, C.W. Schlesinger, P.K. Evaluation of a potential drug interaction between sucralfate and aspirin. Clin.Pharmacol.Ther, 1986, 39, 151-155 [plasma pharmacokinetics extracted metabolites, salicylic acid, salicyluric acid a-phenylcinnamic acid (IS) gradient column temp 30] Mamolo, M.G. Vio, L. Maurich, V. Higb-pressure liquid chromatographic analysis of paracetamol, caffeine and acetylsalicylic acid in tablets. Salicylic acid quantitation. Farmaco.[Prat]., 1985, 40, 111— 123 [tablets simultaneous ac etcuninophen, caffeine, phenazone, salicylic acid]... 

Pedersen, A.K. FitzGerald, G.A. Preparation and analysis of deuterium-labeled aspirin application to pharmacokinetic studies. J.Pharm.Sci., 1985, 74, 188-192 [stability simultaneous salicylic acid] Bevitt, R.N. Mather, J.R. Sharman, D.C. Minimization of salicylic acid formation during preparation of aspirin products for anal3rsis by high-performance liquid chromatography. Analyst, 1984, 109, 1327-1329... 

Nieder, M. Jaeger, H. Selective quantification of doxycychne in human plasma and urine with optimized chromatography. Chromatographia, 1988, 25, 526—530 [column temp 30 plasma urine SPE de-meclocycline (IS) pharmacokinetics non-interfering other tetracyclines, caffeine, nicotine, salicylic acid LOQ 125 ng/mL]... 

Fig. 9.18. The pH-dependent dissolution of salicylic acid (o), benzoic acid ( ), and phenobarbital ( ). (From Gibaldi M. Biopharmaceutics and Clinical Pharmacokinetics, 4th Ed. Philadelphia Lea and Febiger, 1991, with permission.)...

Benfeldt, E., Serup, J., and Menne, T., 1999, Effect of barrier perturbation on cutaneous salicylic acid penetration in human skin in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function, Br. J. Dermatol., 140, 739-748. 

Singh, E and Roberts, M.S., 1993, Dermal and underlying tissue pharmacokinetics of salicylic acid after topical application, J. Pharnutcoldnet. Biopharm., 21, 337-373. 

Di RW, Kolbe K, Merz B, de Vries J, Weber E, Benet LZ. Pharmacokinetics of nicotinic acid-salicylic acid interaction Clin Pharmacol Ther (1989) 46,642-7. 

Colizza, K, Awad M, Kamel A. Metabolism, pharmacokinetics, and excretion of the substance preceptor antagonist CP-122,721 in humans Structural characterization of the novel major circulating metabolite 5-trifluoromethoxy salicylic acid by high-performance liquid chromatography—tandem mass spectrometry and NMR spectroscopy. Drug Metab Dispos 2007 35(6) 884—897. 

The acidic NSAIDs include the salicylates and an increasing number of other compounds. The latter agents, as a group, share many common properties they may have toxicities, are highly protein bound and have the potential for interacting with other protein-bound drugs. The choice of a particular agent often depends on the reaction of the patient. Table 36.3 illustrates pharmacokinetic properties of selected NSAIDs. 

Pharmacokinetics Absorption differs between formulations. Protein binding 50%-80%. Bound to serum albumin. Metabolized to salicylate glucuronides and salicyluric acid. Excreted in urine. 

Thomas, B.R. Fang, X.G. Shen, R Ghodbane, S. Mixed ion pair liquid chromatography method for the simultaneous assay of ascorbic acid, caffeine, chlorpheniramine maleate, dextromethorphan HBr monohydrate and paracetamol in Frenadol sachets. J.Pharm.Biomed.Anal., 1994,12, 85-90 [simultaneous caffeine, chlorpheniramine, dextromethorphan, vitamin C formulations] van der Veen, J. Eissens, A.C. Lerk, C.F. Controlled release of paracetamol from amylodextrin tablets In vitro and in vivo results. Pharm.Res., 1994, 11, 384-387 [plasma pharmacokinetics] Abounassif, M.A. Abdel-Moety, E.M. Gad-Kariem, R.A. HPLC-quantification of diethylamine saliqylate and methyl nicotinate in ointments. J.Liq.Chromatogn, 1992,15, 625-636 [formulations ointments simultabeous diethylamine salicylate, methyl nicotinate acetaminophen is IS simultaneous methyl paraben, propyl paraben... 

E. Pharmacokinetics. Acetylsalicylic acid is well absorbed from the stomach and small intestine. Large tablet masses and enteric-coated products may dramatically delay absorption (hours to days). The volume of distribution of salicylate is about 0.1-0.3 L/kg, but this can be increased by acidemia, which enhances movement of the drug into cells. Elimination is mostly by hepatic metabolism at therapeutic doses, but renal excretion becomes important with overdose. The elimination half-life is normally 2—4.5 hours but as long as 18-36 hours after overdose. Renal elimination is dependent on urine pH. See also Table 11-59 (p 381). 

Oliyai R, Arimilli MN, Jones RJ, Lee WA (2001) Pharmacokinetics of salicylate ester prodrugs of cyclic HPMPC in dogs. Nucleosides Nucleotides Nucleic Acids 20 1411—1414... 

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