NICOTINAMIDE PHARMACOKINETICS IN HUMANS - EFFECT OF GASTRIC-ACID INHIBITION, COMPARISON OF RECTAL VS ORAL-ADMINISTRATION AND THE USE OF SALIVA FOR DRUG-MONITORING

The effect of inhibiting gastric acid secretion on nicotinamide pharma cokinetics 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 s tandard high-performance liquid chromatography (HPLC) method after an oral dose of 3 g of nicotinamide either alone or preceded by pretreatm ent with omeprazole. Suppression of gastric acid production had no sig nificant 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 o bserved than after oral dosing. Thus, no improvement in the pharmacoki netics of nicotinamide was observed using either of these two approach es. Parallel estimations were made using a novel and non-invasive meth od for monitoring nicotinamide pharmacokinetics in saliva. A large and variable fraction of the total amount of nicotinamide-related materia l 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 c hlorhexidine mouthwash, indicating that the oral Bora was responsible for its production. The time to peak levels of nicotinamide or of nico tinamide plus nicotinic acid in saliva correlated well with that in pl asma. However, peak concentrations for nicotinamide alone were signifi cantly lower than in plasma, and very variable, whereas for nicotinami de plus nicotinic acid saliva levels were 20-30% higher, but more cons istent. Although there ale some practical difficulties in quantitative ly handling saliva, the method is very useful for monitoring nicotinam ide pharmacokinetics and for assessment of compliance with nicotinamid e treatment.