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Disposition of single-dose intravenous and oral aspirin in children
S Ito1, R Oka, A Tsuchida
1Department of Pediatrics, Asahikawa Medical College, Japan.
Insights
Oral aspirin provides longer exposure to acetylsalicylic acid (ASA) than intravenous aspirin in children with Kawasaki disease. While both routes yield similar salicylic acid levels, oral ASA results in higher ASA concentrations, with unclear clinical significance.
Area of Science:
- Pharmacology
- Pediatrics
- Cardiology
Background:
- Kawasaki disease (KD) is a pediatric inflammatory condition affecting coronary arteries.
- Aspirin (acetylsalicylic acid) is a common treatment for KD, with oral and intravenous formulations available.
- Understanding the pharmacokinetics of different aspirin formulations is crucial for optimizing pediatric treatment.
Purpose of the Study:
- To compare the pharmacokinetics of acetylsalicylic acid (ASA) and salicylic acid (SA) following oral (buffered aspirin tablets) and intravenous (aspirin DL-lysine) administration in children with prior KD.
- To evaluate differences in drug exposure, absorption, and elimination between the two administration routes.
Main Methods:
- Pharmacokinetic analysis of acetylsalicylic acid and salicylic acid in 5 children with a history of Kawasaki disease.
- Administration of buffered aspirin tablets (oral) and intravenous aspirin DL-lysine.
- Measurement of key pharmacokinetic parameters including mean residence time (MRT), elimination half-life (t1/2), and area under the curve (AUC).
Main Results:
- Oral aspirin demonstrated a longer mean residence time (1.18 h vs. 0.37 h) and elimination half-life (40 min vs. 17 min) for acetylsalicylic acid compared to intravenous aspirin.
- Absorption of oral aspirin resulted in 51% intact ASA and 23% conversion to SA presystemically, totaling 74% absorption.
- Intravenous administration required approximately 70% of the oral dose to achieve equivalent salicylic acid concentrations, but oral administration led to a 1.5-fold higher area under the curve for acetylsalicylic acid.
Conclusions:
- Oral aspirin administration leads to prolonged exposure to acetylsalicylic acid in children with prior Kawasaki disease compared to intravenous administration.
- While intravenous aspirin may require a lower dose for equivalent salicylic acid levels, oral aspirin results in significantly higher acetylsalicylic acid exposure.
- The clinical implications of these pharmacokinetic differences in acetylsalicylic acid exposure remain to be determined.
Abstract:
We described the pharmacokinetics of acetylsalicylic acid and salicylic acid in 5 children with prior Kawasaki disease receiving buffered aspirin tablets or intravenous aspirin DL-lysine. Oral aspirin is characterized by its longer mean residence time in the body (MRT), an indicator for duration of exposure, than intravenous aspirin (1.18 vs. 0.37 h). The apparent elimination half-life (t1/2) of acetylsalicylic acid was also longer after oral than after intravenous administration of aspirin (40 vs. 17 min). The mean absorption time was calculated to be as long as 0.8 h. In contrast, the two modes of administration gave virtually identical results regarding MRT of salicylic acid proper and its t1/2. After oral administration of aspirin, 51% of the dose is absorbed intact as acetylsalicylic acid while 23% is converted to salicylic acid presystemically, indicating that 74% of aspirin is actually absorbed. Our data suggest that an equivalent intravenous aspirin dose to achieve the same salicylic acid concentration is about 70% of the oral dose. However, the area under the curve of acetylsalicylic acid itself, a more potent cyclooxygenase inhibitor than salicylic acid, would be about 1.5 times higher than that following oral administration. The clinical consequences of this exposure difference remain uncertain.