PARACETAMOL PHARMACOKINETICS ARE INDEPENDENT OF CALORIC-INTAKE AND PHYSICAL-ACTIVITY

Regular physical activity provokes numerous adaptations in the gastroi ntestinal tract and liver. It has been suggested that these changes ma y alter the pharmacokinetics of drugs in humans. We addressed this sug gestion by measuring paracetamol pharmacokinetics in a group of health y young males chosen to represent the widest possible range of habitua l physical activity and food intake. Daily caloric intake in the 19 me n, 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 wi th physical activity or with caloric intake: (a) for the parent compou nd, there was no correlation in maximum blood concentrations, half-lif e, total clearance, or area under the curve with individual caloric in take, and (b) when volunteers were divided a priori into more active a nd less active groups, or a posteriori into higher and lower calorie c onsumers (a 70% difference in daily caloric intake), these groups had identical plasma disappearance curves for paracetamol itself and for b oth of its metabolites. We conclude that the enormous variation among humans in long term physical activity and food intake fails to alter a ny aspect of the appearance or disappearance of paracetamol from blood .