Effects of chlorpromazine and atropine on acetaminophen absorption in rabbits

The effects of chlorpromazine and atropine on the gastrointestinal absorption of acetaminophen were investigated in rabbits. Two doses of chlorpromazine and atropine were injected intraperitoneally 30 min prior to the oral administration of acetaminophen. Blood samples were collected before and 0.25,0.5,0.75, 1.0,1.5,2,3,4,5 and 6 h after acetaminophen administration and were analyzed for acetaminophen contents using a HPLC method. Chlorpromazine at a 10 mg/kg dose significantly reduced the maximum plasma concentration (C_max) of acetaminophen from 64.2 ± 2.8 to 40.0 ± 6.3 μgg/ml(P < 0.05). In addition, chlorpromazine at 5 and 10 mg/kg doses significantly increased the time taken to reach the maximum plasma concentration (T_max) of acetaminophen from 0.29 ± 0.04 to 0.67 ± 0.15 and 0.96 ± 0.21h, respectively (P < 0.05). Atropine at 0.5 and 1.0 mg/kg doses also significantly reduced the C_max of acetaminophen from 69.6 ± 4.7 to 45.6 ± 3.7 and 45.9 ± 6.7 μg/ml, respectively (P < 0.05). However, atropine has little effect on T_max of acetaminophen. Both chlorpromazine and atropine did not seem to affect the area under the plasma concentration-time curve and the elimination half-life of acetaminophen. It was concluded that chlorpromazine and atropine affect the rate but not the extent of acetaminophen absorption, by delaying the gastric emptying.