Sex-Related Differences In Aspirin Pharmacokinetics Following IV Injection In Rabbits
Clinical and experimental studies suggest that aspirin (ASA) is a useful antithrombotic agent; however, its efficacy seems limited to males. This may be due to differences in i) the effects of ASA on platelets and/or vessel wall or ii) the pharmacokinetics of ASA, between males and females.We examined the possible sex-related differences in 1) enhanced arterial thrombosis 3 h after treatment with 0, 3, 10 or 100 mg/kg ASA and 2) the distribution (α) and clearance (β) of ASA between male and female rabbits. Enhanced arterial thrombosis was determined by measuring 51Cr-platelet accumulation onto injured carotid arteries. ASA-plasma levels were determined, using a GC/MS assay. 51Cr-platelet accumulation onto injured arteries was 0.67 ± 0.15 × 106 (males) and 0.52 ± 0.07 × 106/100 mm2 vessel wall (females; mean ± SEM, n=8). 3 mg/kg ASA had no effect. 10 and 100 mg/kg ASA significantly enhanced 5lcr- platelet accumulation to 1.94 ± 0.41 × 106 and 2.59 ± 0.93 × 106 in males, and to 1.65 ± 0.32 × 106 and 2.16 ± 0.73 × 106 in females (p<0.001). There were no sex-related differences.ASA-plasma levels were determined in serial samples collected from 10 rabbits injected with 10 mg/kg ASA. One week later, the study was repeated in the same animals. The α and β T½’s were 3.3 ± 0.2 and 29.2 ± 3.0 (min) respectively in males after the 1st treatment. Similar T½’s were found after the 2nd treatment (3.4 ± 0.1, 23.3 ± 3.5 respectively). In females, the initial α and β T½’s were 3.7 ± 0.2 and 26.1 ± 3.5 respectively. The α T½ was similar (3.6 ± 0.1) whereas the β T½ was significantly decreased (14.8 ± 0.3, p<0.007) after the 2nd ASA treatment. This decrease in females was associated with an increase in the apparent volume of distribution, p<0.02The significance of these findings is uncertain.