The pharmacokinetics of acetylsalicylic acid (ASA, 650 mg.) and salicylic acid (SAY 500 mg.) were studied following intravenous administration in males. The resultant plasma concentration-time curves were described by bi-exponential equations. The half-life of the first exponent was 2-5 min. for both compounds while that of the second exponent was 13-19 min. and 3.5-4.5 hr. for ASA and SAY respectively. Over the dose range 0.3-1.2 g. ASA, the area under the ASA plasma concentration-time curve was proportional to the dose administered. Also SA was shown to be the exclusive metabolite of ASA. Analysis of the resent results, over the dose range and duration of study, showed that the data c o d 8 best be fitted by conceiving the body to act as a two-compartmental open system with respect to these drugs. The significance of these findings on measurement of the rate constants of metabolism, volume of distribution, and other pharmacokinetic parameters are discussed.
T IS an interesting fact that, although acetyl-I salicylic acid (ASA) has been consumed in tremendous quantities since its introduction in 1899, only scant information is available pertaining to the pharmacokinetics of this drug in man. This is all the more surprising as the salicylates have been the subject of two monographs (1, 2) and a symposium (3). Essentially, the problem has been an analytical one in that previous assays either did not differentiate between ASA and its metabolite, salicylic acid (SA), or estimated ASA as the increase in SA upon hydrolysis of the sample (4, 5), which is at best an insensitive method. More recently attempts have been made to increase the specificity of the assay using paper chromatography or selective extraction (6, 7).
Although ASA is known to be rapidly metabolized to SA i n vivo, only the mean data of Leonards (8) and Lange and Bell (6) allow any estimate for the apparent elimination half-life, and values of 17 min. and 30 min. are obtained, respectively. However, in both studies, the drug was given orally so that estimates could be influenced by continued absorption of ASA during the decline of drug blood levels. The total urinary recovery of ASA as SA or its metabolites (9) suggests that SA is the only metabolite of ASA while 1.5% has been reported to be excreted unchanged in the urine of man (10). Much more information is available relating to SA owing to its high plasma levels, relatively long half-life, and ease of analysis (1-3). Nevertheless, there