Chronopharmacokinetics of acetaminophen in healthy human volunteers

Summary

Acetaminophen is a common antipyretic-analgesic drug usually administered orally any time of the day. It was however claimed by Belanger et al, (1985) to have a longer elimination half-life (t_1/2β) in rats when administered by 2100 h, than at 0700 h. This work is designed to investigate this claim in man and to study the circadian changes in acetaminophen pharmacokinetics at three dosing times; 0730 h, 1300 h and 2100 h. Seven healthy male volunteers, age 26.28±3.01 years, weighing 65.00±2.2 kg, were administered with 1000 mg oral acetaminophen at the three circadian time after a period of fast of not less than 4 h. The pharmacokinetic values obtained, though varied, are found to be in similar ranges with previously reported values. The absorption parameters ka and mean T_max were significantly altered with dosing at 0730 h and 2100 h while the mean t_1/2α and ka were also significantly changed. There was a significant difference (P<0.05) between the T_max values obtained at 2100 h and that of 0730 h, while the 34.9% increase at dosing time 1300 h over 0730 h dosing times is not statistically significant (P>0.05). C_max was found to be 22.31±4.24 mcg/ml for 0730h dosing time, while a decrease of 9.64 and 11.7% over this value was recorded for dosing time 1300 h and 2100 h respectively. The changes are however not statistically significant (P>0.05). AUC_o−a at 0730 h did not show any significant change when compared with values obtained at 1300 h and 2100 h, but there was a significant difference between the values obtained at 1300 h and 2100 h. Elimination half-life, t_1/2β was found to be 1.68±0.67 h at 0730 h. There was an increase of 13.1% and 20.83% over this value at 1300 h and 2100 h. These increases were not statistically significant (p>0.05). Although there are similar increases in t_1/2β at the 1300 h and 2100 h dosing time as reported by Belanger et al 1985, the increases were not statistically significant in man.