The question concerns the bioavailability of acetylsalicylic acid from suppositories as compared wi

Fråga: The question concerns the bioavailability of acetylsalicylic acid from suppositories as compared with tablets. Background: the present policy is to give 500 mg of acetylsalicylic acid as a suppository postoperatively to patients who have had heart surgery. Thereafter, they receive a daily dose of 75-160 mg as tablets.

Sammanfattning: There is no documentation available concerning the bioavailability of acetylsalicylic acid suppositories as they are prepared in Swedish pharmacies. It can be assumed that the release of acetylsalicylic acid from a suppository is subject to many physiological and pharmaceutical factors, such as the particle size of the drug substance and the characteristics of the suppository base. There are a few studies in which oral and rectal dosage forms are compared, but information concerning the bioavailability is not always complete. Studies in which only the salicylate levels were measured indicate for this compound a relative bioavailability of 60-75 per cent after rectal administration of aspirin compared with tablets. Only one study could be found in which both acetylsalicylic acid and salicylate levels were measured and compared between a tablet and a suppository of aspirin. A relative bioavailability of 93 per cent for acetylsalicylic acid was found after rectal administration. Based on this study, a dose of 500 mg in a suppository seems relatively high if the purpose is to obtain complete inhibition of platelet aggregation. A fully reliable answer could however only be obtained from a clinical trial.

Svar: The absorption of aspirin (acetylsalicylic acid) after oral administration of a solution is usually complete, while enteric-coated tablets are less reliably absorbed (1). The absorption of aspirin as regular tablets is intermediate between that of a solution and that of enteric-coated tablets and is usually greater than 80 per cent (1).

Following oral administration, some acetylsalicylic acid is hydrolysed to salicylate (salicylic acid) in the wall of the intestine (2). After absorption, acetylsalicylic acid is also rapidly converted into salicylate. The plasma half-life of acetylsalicylic acid is 15-20 minutes. Salicylate is mainly eliminated by hepatic metabolism. The formation of the major metabolites, salicyluric acid and salicyl phenolic glucuronide, is easily saturated and follows Michaelis-Menten kinetics; following a 300 mg dose of acetylsalicylic acid, the half-life of salicylic acid is around 3h, after a one gram dose around 5-6h (1,2). Both acetylsalicylic acid and salicylate have pharmacological activity, but only acetylsalicylic acid has an anti-platelet effect (2).

In general, the release of a drug from a suppository may be influenced by many physiological and pharmaceutical factors, such as amount, composition and pH of rectal fluid, the particle size of the drug substance and the characteristics of the suppository base (3).

Acetylsalicylic acid suppositories as they are prepared by the Swedish pharmacies contain the following substances: acidum acetylsalicylicum 500 mg; silica colloidalis anhydrica 16 mg; adeps solidus 1600 mg. There is no documentation available concerning the bioavailability of this specific preparation (4). However, a number of studies comparing the bioavailability of aspirin tablets and suppositories prepared with other bases have been done.

One study (5) compared serum salicylic levels in 12 neurosurgical patients after rectal and oral administration of one gram of acetylsalicylic acid. The type of suppository used in this study was not further specified. The mean relative bioavailability from a suppository compared with that of a tablet was 76 per cent after the rectal administration. The mean t-max (time to reach the maximum serum level) was significantly longer (3.75h vs 2.58h) and the mean C-max (the maximum serum level) was significantly lower (197 vs 296 umol/l) after rectal administration compared with oral administration; the suppository caused delayed absorption with no clear peak levels. A similar pharmacokinetic pattern was seen in other studies as well.

Another study (6) compared plasma levels of salicylic acid after both oral and rectal administration of a 300 mg dose of acetylsalicylic acid. The suppository used contained the substance Imhausen. (Imhausen is a suppository base formulation made from medium-chain triglycerides with the trade name Witepsol.)

The plasma salicylate levels were also investigated after oral and rectal administration of a dose of 600 mg acetylsalicylic acid in volunteers and in patients with fever (7). Suppositrin (a variety of Witepsol base) was used as a base for the suppositories. It was found that the C-max for suppositories in volunteers was 56 per cent of the C-max obtained with the tablets. In patients with fever a relative C-max of 74 per cent was obtained. However, no further information concerning the bioavailability was given, except that the AUC for the suppository in volunteers was significantly lower than the AUC for the tablet.

It should be stressed that in the studies mentioned so far, only salicylate levels were measured and not the levels of acetylsalicylic acid or the metabolites of salicylate. Only one study could be found in which plasma levels of acetylsalicylic acid, salicylic acid, salicyluric acid and codeine were monitored after intravenous, oral and rectal application of a preparation containing acetylsalicylic acid 500 mg and codeine 40 mg (8). The mean absolute bioavailability of acetylsalicylic acid was 68 per cent after oral application and 60 per cent after rectal application, meaning a relative bioavailability of 93 per cent of acetylsalicylic acid after rectal administration.