NICOTINAMIDE PHARMACOKINETICS IN NORMAL VOLUNTEERS AND PATIENTS UNDERGOING PALLIATIVE RADIOTHERAPY

The influence of nicotinamide formulation on absorption characteristic s and incidence of adverse side-effects has been studied in normal vol unteers and in patients undergoing radiotherapy. Escalating single or repeated oral doses of nicotinamide were administered in tablet or liq uid form under fasting or non-fasting conditions. Drug absorption was slowed both by the presence of food in the stomach and by the administ ration of nicotinamide in tablet form compared with when it was dissol ved in orange juice, Peak concentrations were generally slightly highe r following the liquid preparation, but the incidence of adverse side- effects (chiefly nausea) was increased, A single dose of 9 g (88-97 mg /kg) nicotinamide in tablet form was well tolerated in two fasting nor mal volunteers, and in patients, doses of up to 133 mg/kg as tablets w ere tolerated twice/week for three weeks, Daily administration of 80 m g/kg nicotinamide was tolerated when given as tablets, but not ina liq uid formulation, Neither the peak concentration nor the area under the concentration/time curve (AUC) of nicotinamide, nor the main metaboli tes of nicotinamide appeared to correlate with the incidence of toxici ty.