Antipyrine clearance in patients with Gilbert's syndrome

The pharmacokinetic parameters of antipyrine (AP) were examined in 45 normal healthy subjects (18 heavy smokers, 5 mild smokers, and 22 nonsmokers) and in 12 patients with Gilbert's syndrome (GS), amongst whom 2 mild and 1 heavy smokers were included. Heavy smokers were defined as persons smoking more than 20 cigarettes/day and mild smokers as those smoking less than 10 cigarettes/day. Significant differences (unpaired Student's t-test) in the elimination t1/2 of AP among the study groups and in its total plasma clearance (CL) were observed without any change in the apparent volume of distribution. The individual CL values varied within the same study groups, but the mean +/- SD (0.026 +/- 0.004 l/h/kg) in the GS patients did not significantly differ from that in normal nonsmokers (0.025 +/- 0.006 l/h/kg) or in normal mild smokers (0.028 +/- 0.001 l/h/kg). When the 3 patients with GS who smoked were excluded, the mean CL of the group (0.025 l/h/kg) was again comparable to that of the normal nonsmokers and mild smokers. The mean (+/- SD) CL in normal heavy smokers (0.040 +/- 0.012 l/h/kg) was significantly greater than in normal mild smokers (p less than 0.05), in normal nonsmokers (p less than 0.001) and in patients with GS (p less than 0.001). The results suggest that drug oxidation capacity estimated from the total plasma CL of AP appears unimpaired in GS.