ANTIPYRINE DISPOSITION IN OBESITY - EVIDENCE FOR NEGLIGIBLE EFFECT OFOBESITY ON HEPATIC OXIDATIVE-METABOLISM

Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) wer e significantly greater in the obese than in the lean group. (Mean 110 .4 vs 62.7 kg; 38.5 vs 22.3 kg . m(-2) and 181vs 106% respectively). I n a subgroup of 6 obese subjects (group C) antipyrine was given again 11.3 months later after a 29.8 kg mean weight loss. Antipyrine apparen t volume of distribution (V) and elimination half-life (t(1/2)) were s ignificantly greater in the obese than in the lean group (V 49.9 vs 34 .31 respectively; t(1/2) 15.5 vs 12.0 h respectively), but its clearan ce rate (CL(o)) values were similar. V corrected for total body weight was significantly reduced in group A than in group B (0.45 vs 0.551 . kg(-1) respectively). Stratified comparison of antipyrine pharmacokin etics between obese and lean subjects according to age, gender and smo king habits did not alter the overall results. In group C, weight redu ction was associated with a significant decrease in antipyrine V (from 51.8 to 47.51) and t(1/2) (from 15.1 to 12.7 h), and a non-significan t increase in antipyrine CL(o). We conclude that in severely obese sub jects, antipyrine total V is mildly increased but V corrected for tota l body weight is significantly decreased. In addition, obesity is asso ciated with a slight prolongation of antipyrine t(1/2) whereas its CL( o) is unaltered. These findings may indicate that obesity, even in its extreme form, has a negligible effect on the oxidative metabolic capa city of the liver.