Stratford M R, Dennis M F, Hoskin P J, Saunders M I, Hodgkiss R J, Rojas A
Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex, England.
Acta Oncol. 1996;35(2):213-9. doi: 10.3109/02841869609098504.
The influence of nicotinamide formulation on absorption characteristics and incidence of adverse side-effects has been studied in normal volunteers and in patients undergoing radiotherapy. Escalating single or repeated oral doses of nicotinamide were administered in tablet or liquid form under fasting or non-fasting conditions. Drug absorption was slowed both by the presence of food in the stomach and by the administration of nicotinamide in tablet form compared with when it was dissolved in orange juice. Peak concentrations were generally slightly higher 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 normal volunteers, and in patients, doses of up to 133 mg/kg as tablets were tolerated twice/week for three weeks. Daily administration of 80 mg/kg nicotinamide was tolerated when given as tablets, but not in a liquid formulation. Neither the peak concentration nor the area under the concentration/time curve (AUC) of nicotinamide, nor the main metabolites of nicotinamide appeared to correlate with the incidence of toxicity.
在正常志愿者和接受放疗的患者中，研究了烟酰胺制剂对吸收特性和不良反应发生率的影响。在禁食或非禁食条件下，以片剂或液体形式递增单次或重复口服烟酰胺剂量。与溶解在橙汁中相比，胃中存在食物以及以片剂形式给药烟酰胺都会使药物吸收减慢。液体制剂后的峰值浓度通常略高，但不良反应（主要是恶心）的发生率增加。两名禁食的正常志愿者对单次9 g（88 - 97 mg/kg）片剂形式的烟酰胺耐受性良好，在患者中，高达133 mg/kg的片剂剂量每周服用两次，持续三周也能耐受。以片剂形式每日给予80 mg/kg烟酰胺可耐受，但液体制剂则不能。烟酰胺的峰值浓度、浓度/时间曲线下面积（AUC）以及烟酰胺的主要代谢产物似乎均与毒性发生率无关。
