Paracetamol Pharmacokinetics are Independent of Caloric Intake and Physical Activity

Abstract

SummaryRegular physical activity provokes numerous adaptations in the gastrointestinal tract and liver. It has been suggested that these changes may alter the pharmacokinetics of drugs in humans. We addressed this suggestion by measuring paracetamol pharmacokinetics in a group of healthy young males chosen to represent the widest possible range of habitual physical activity and food intake. Daily caloric intake in the 19 men, obtained from 3-day dietary records, ranged from 1680 to 5110 kcal (21 to 66 kcal/kg). Each volunteer ingested paracetamol 1000mg in the fasted, resting state in the morning; antecubital venous blood samples were analysed for the parent compound and its glucuronide and sulfate conjugates by high-performance liquid chromatography for 6 subsequent hours. We found no evidence that paracetamol pharmacokinetics vary with physical activity or with caloric intake: (a) for the parent compound, there was no correlation in maximum blood concentrations, half-life, total clearance, or area under the curve with individual caloric intake, and (b) when volunteers were divided a priori into more active and less active groups, or a posteriori into higher and lower calorie consumers (a 70% difference in daily caloric intake), these groups had identical plasma disappearance curves for paracetamol itself and for both of its metabolites. We conclude that the enormous variation among humans in long term physical activity and food intake fails to alter any aspect of the appearance or disappearance of paracetamol from blood.Recent studies in humans and animals provide evidence that regular physical activity, perhaps via its associated hyperphagia, provokes increases in intestinal transit rates, hepatic biotransformation enzyme content, bile flow rate, and biliary clearance of certain test substances.[l-3] These latter studies suggest that habitual physical activity in humans could alter the pharmacokinetics of drugs. Past infonnation in this regard has been equivocalJ4] Some, but not all, studies of the relationship of physical activIty to 14C-aminopyrine clearance suggest that habitually elevated physical activity enhances total clearance of this compoundJ5,6] Similarly, there is contradictory evidence regarding the influence of regular exercise on hexobarbital sleeping time in ratsJ3,7] Recent data suggest that 6 weeks of habitual voluntary exercise in rats increases the total and biliary clearances of paracetamol and enhances the biliary elimination of the paracetamol-sulfate con-

Influence of Diet and Nutritional Status on Drug Metabolism

“…In healthy individuals the total clearance of paracetamol was found unrelated to differences of energy supply ranging from 1680 to 5110 kcal/day. [94] However, these data were not obtained by an intraindividual comparison of the effects of diet variation, but by group comparison.…”