Stratford M R, Dennis M F, Hoskin P, Phillips H, Hodgkiss R J, Rojas A
Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex, UK.
Br J Cancer. 1996 Jul;74(1):16-21. doi: 10.1038/bjc.1996.309.
The effect of inhibiting gastric acid secretion on nicotinamide pharmacokinetics was studied in five volunteers with the intent of reducing the large variations observed previously in the time to and magnitude of peak plasma concentrations. Plasma levels were determined using a standard high-performance liquid chromatography (HPLC) method after an oral dose of 3 g of nicotinamide either alone or preceded by pretreatment with omeprazole. Suppression of gastric acid production had no significant effect on the rate of uptake or on the peak levels achieved. To bypass gastric acidity, the rectal route was also assessed using a suppository in four volunteers and one patient undergoing radiotherapy. Absorption was slow and variable and much lower plasma levels were observed than after oral dosing. Thus, no improvement in the pharmacokinetics of nicotinamide was observed using either of these two approaches. Parallel estimations were made using a novel and non-invasive method for monitoring nicotinamide pharmacokinetics in saliva. A large and variable fraction of the total amount of nicotinamide-related material in saliva was found to be nicotinic acid, a metabolite not normally found in human plasma. This conversion was inhibited by the use of a chlorhexidine mouthwash, indicating that the oral flora was responsible for its production. The time to peak levels of nicotinamide or of nicotinamide plus nicotinic acid in saliva correlated well with that in plasma. However, peak concentrations for nicotinamide alone were significantly lower than in plasma, and very variable, whereas for nicotinamide plus nicotinic acid saliva levels were 20-30% higher, but more consistent. Although there are some practical difficulties in quantitatively handling saliva, the method is very useful for monitoring nicotinamide pharmacokinetics and for assessment of compliance with nicotinamide treatment.
在五名志愿者中研究了抑制胃酸分泌对烟酰胺药代动力学的影响，目的是减少先前观察到的血浆峰浓度出现时间和幅度的巨大差异。口服3 g烟酰胺后，单独或在奥美拉唑预处理后，使用标准高效液相色谱（HPLC）方法测定血浆水平。胃酸分泌的抑制对摄取速率或达到的峰值水平没有显著影响。为了避开胃酸，还在四名志愿者和一名接受放疗的患者中使用栓剂评估了直肠给药途径。吸收缓慢且多变，观察到的血浆水平比口服给药后低得多。因此，使用这两种方法均未观察到烟酰胺药代动力学的改善。使用一种监测唾液中烟酰胺药代动力学的新型非侵入性方法进行了平行评估。发现唾液中与烟酰胺相关物质总量的很大一部分且变化不定的部分是烟酸，这是一种在人血浆中通常不存在的代谢物。使用洗必泰漱口水可抑制这种转化，表明口腔菌群是其产生的原因。唾液中烟酰胺或烟酰胺加烟酸的峰值水平出现时间与血浆中的相关性良好。然而，单独烟酰胺的峰值浓度明显低于血浆，且变化很大，而烟酰胺加烟酸的唾液水平则高20 - 30%，但更一致。尽管在定量处理唾液方面存在一些实际困难，但该方法对于监测烟酰胺药代动力学和评估烟酰胺治疗的依从性非常有用。
