What doses of oral aspirin is equivalent to rectal aspirin?

Comment by InpharmD Researcher

There appears to be a lack of direct conversion from oral to rectal aspirin. In general, absorption of rectal aspirin is inconsistent and often lower than oral, varying by brand, formulation, and retention time. In one prospective study, a 600 mg suppository produced more efficient absorption than 162 mg chewed aspirin, suggesting that a higher rectal dose may be needed to match an oral dose (see Table 1). Older pharmacokinetic studies in adults showed that only 20-40% of a rectal aspirin dose was absorbed after 2 hours, with absorption improving over longer retention and varying depending on the suppository base. Overall, these findings indicate that systemic availability from rectal aspirin is variable, and prolonged retention or higher doses may be needed to achieve levels comparable to oral administration.

Background

A 2009 commentary reviewed the emerging use of aspirin in cardiovascular disease, specifically comparing oral dosing with rectal suppositories. The article highlighted a crossover study (see Table 1) in which 24 healthy volunteers received 162 mg oral aspirin (chewed) and 600 mg rectal suppositories, with salicylic acid levels measured at baseline, 30, 60, and 90 minutes. Results showed that both routes achieved systemic salicylic acid exposures within 90 minutes, indicating effective absorption. Peak aspirin levels occurred earlier with rectal dosing (as soon as 30 minutes) compared to oral dosing (60 minutes), suggesting relatively rapid systemic availability via the rectal route. Suppression of platelet aggregation was similar between the two routes, though some variability in absorption was noted. The commentary emphasized that rectal administration avoids first-pass hepatic metabolism, potentially allowing for earlier aspirin bioavailability. Based on these findings, the authors of the commentary suggest that stroke patients unable to take oral aspirin may potentially be candidates for an initial rectal aspirin suppository until an alternative feeding method is established. [1]

A dated 1975 investigation assessed the bioavailability of salicylate from different brands of commercially available aspirin rectal suppositories, each containing approximately 600 to 650 mg of aspirin. The study focused on adult subjects and highlighted the slow absorption profiles of these formulations compared to the oral administration of aspirin tablets. It was observed that, on average, at best, only about 40% of the administered dose was absorbed when the retention time in the bowel was limited to 2 hours. The research further noted that four out of the five products tested exhibited significantly lower absorption rates, averaging just around 20% bioavailability. The research utilized a cohort of adult male volunteers aged 24 to 35, who were instructed to insert the suppository in the morning and either evacuate their bowels after exactly 2 hours or retain the suppository for as long as possible beyond that, though retention times varied between 11 to >24 hours. Analytical methods involved collecting urine samples over a period of 28 to 32 hours and analyzing for total salicylate using a spectrophotometric method. The findings underscored that the brands coded L demonstrated the highest absorption rate compared to others (38%), yet absorption remained notably low unless retention times extended beyond 10 hours, revealing the substantial impact of retention time on drug availability. Despite the study's comprehensive comparative analysis and variation amongst different brands, the overall findings indicate that rectal suppositories delivered significantly reduced and slower aspirin absorption compared with oral administration, with only partial availability when retention time was restricted. [2]

A 1971 pharmacokinetic experiment examined the absorption of salicylates from rectal suppositories compared to oral administration. During the first phase of the study, twelve healthy adult subjects (10 male, 2 female), weighing 52 to 84 kg, received either aspirin 600 mg or sodium salicylate 534 mg orally upon arising. After 1 week, the subjects received suppositories containing the same doses of aspirin or sodium salicylate. Six different suppository bases incorporating aspirin and sodium salicylate were utilized. The subjects were ambulatory and permitted to eat and drink normally. Urine samples were collected every 2 hours after dosing and analyzed. Results showed that rectal administration of these drugs was equivalent to oral doses. However, the rate and extent of absorption were influenced by the choice of suppository base. Rapid release of aspirin was observed from suppositories made from polyethylene glycol and polyoxyethylene sorbitan monostearate with glyceryl monostearate, whereas aspirin release was suboptimal from sorbitan monopalmitate. Conversely, sodium salicylate demonstrated efficient release from a theobroma oil base. The polyethylene glycol suppositories released aspirin rapidly, yielding absorption profiles comparable to oral administration, while theobroma oil favored sodium salicylate release at body temperature, aligning with rapid systemic absorption. Overall, these findings underscore the importance of physicochemical properties and formulation factors in optimizing the rectal administration of analgesic drugs. [3]

References:

[1] Pesola GR. Emergent aspirin use in cardiovascular disease in the emergency department: oral dosing versus rectal suppositories. Acad Emerg Med. 2009;16(2):162-164. doi:10.1111/j.1553-2712.2008.00338.x
[2] Gibaldi M, Grundhofer B. Bioavailability of aspirin from commercial suppositories. J Pharm Sci. 1975;64(6):1064-1066. doi:10.1002/jps.2600640649
[3] Parrott EL. Salicylate absorption from rectal suppositories. Journal of Pharmaceutical Sciences. 1971;60(6):867-872. doi:10.1002/jps.2600600613

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What doses of oral aspirin is equivalent to rectal aspirin?

Level of evidence

X - No data  Read more→



Please see Table 1 for your response.


A Comparison of Salicylic Acid Levels in Normal Subjects after Rectal versus Oral Dosing

Design

Prospective cohort study

N= 24

Objective

To compare the serum salicylic acid levels of aspirin administered orally and rectally over time in healthy adult subjects

Study Groups

Oral administration (n= 24)

Rectal administration (n= 24)

Inclusion Criteria

Healthy, nonpregnant, adult volunteers without active illness, who did not take any medication regularly

Exclusion Criteria

None reported

Methods

Each subject served as their own control. On the first day, 162 mg of oral aspirin was chewed and swallowed. Salicylic acid levels were obtained at baseline and then 30, 60, and 90 minutes after dosing. The 600-mg aspirin suppository was self-administered 1 week later with samples drawn at the same intervals.

Duration

2 days, separated by a 1-week washout period

Outcome Measures Primary: Serum salicylic acid levels over time
Baseline Characteristics  

All subjects (n= 24)

Age, mean years 27
Gender - Male 16
Gender - Female 8
Ethnicity - Asian American 2
Ethnicity - African American 1
Results  

Oral Administration

Rectal Administration p-value
Mean salicylic acid levels from baseline to 30 minutes No significant difference

No significant difference

>0.05
Mean salicylic acid levels from 30 to 60 minutes

Lower

Higher <0.001
Mean salicylic acid levels from 60 to 90 minutes

Lower

Higher 0.002
Subjects with increasing salicylic acid levels

29%

>60% -
Subjects with fast response

33%

N/A -

Findings were mainly presented in figures, limiting the amount of detail conveyed in the text.

Adverse Events

No adverse outcomes to the aspirin doses were reported in any subjects

Study Author Conclusions

The rectal administration of a 600-mg suppository provides sufficient levels of salicylic acid within 90 minutes to meet or exceed that of oral aspirin. Whether these results translate into better clinical outcomes is unknown.

Critique

The study was well-designed with subjects serving as their own controls, reducing confounding factors. However, the small sample size and lack of clinical outcome data limit the generalizability of the findings. Additionally, the study did not address the potential side effects of higher rectal doses.


References:

Maalouf R, Mosley M, James Kallail K, Kramer KM, Kumar G. A comparison of salicylic acid levels in normal subjects after rectal versus oral dosing. Acad Emerg Med. 2009;16(2):157-161. doi:10.1111/j.1553-2712.2008.00318.x