The influence of food on nitrofurantoin bioavailability

Abstract

The effect of food on the absorption of five commercial dosage forms of nitrofurantoin varying widely in drug release and dissolution characteristics was assessed in man after oral administration. Four healthy fasting and nonfasting male subjects received, in a crossover fashion, a single 100-mg dose of microcrystalline nitrofurantoin as an aqueous suspension, three different compressed tablets, and a single 100-mg dose of macrocrystalline nitrofurantoin in a capsule. Both the absorption and the duration of therapeutic urinary concentrations of nitrofurantoin were significantly increased after administration of the five products to nonfasting subjects. The enhancement in the bioavailability of the drug in the presence of food ranged from 20% to 400%, with the greatest absorption-enhancing effect occurring with those dosage forms exhibiting the poorest dissolution characteristics. It is concluded that single-dose comparative bioavailability studies of drug products normally administered with food should be performed in both nonfasting and fasting subjects.

The effects of food on drug bioavailability.

“…This effect is maximal for those formulations of the drug with the poorest dissolution characteristics, suggesting that the effect is at least in part due to better dissolution resulting from delayed gastric emptying (Rosenberg & Bates, 1976). In contrast to these observations concerning nitrofurantoin, the bioavailability of the newer quinolone antibiotics (e.g.…”

The influence of nutrition on the systemic availability of drugs. Part I: Drug absorption

“…The temporal relation of drug to carbohydrate absorption is important for the therapeutic efficacy of other sulfonylureas too [108], and is regularly given special attention in insulin therapy. The opposite effect of coingestion of a meal was reported in an investigation using nitrofurantoin [98]: when five preparations with different in vitro dissolution characteristics were administered fasting, the extent of systemic availability varied greatly. When the medication was taken after a meal, these differences subsided to a major degree: the extent of systemic availability was enhanced, the increment being the largest in those preparations, which gave the lowest fasting results and the most unfavorable in vitro dissolution data.…”

“…Dietary fat has been considered as a factor facilitating the dissolution and thereby increasing the absorption of lipophilic compounds [1,32,72,77,79,81]. However, observations using various brands of spironolactone, nitrofurantoin, but possibly also theophyline suggest, that the effect of a fatty meal to a major extent is a consequence of prolonged gastric retention, ensuring sufficient time for the active compound to be released from the various pharmaceutical formulations [63,80,98]. Possible effects of carbohydrates and protein on drug absorption [39, 51, 56, 59, 67, 76, 77, 109] can be best explained as indirect effects on gastric emptying, being related to the energy density and the osmolarity of the intragastric solution of sugars and amino acids or peptides; these may have been ingested as such, or may arise from the intragastric hydrolysis of polysaccharides and polypeptides.…”

Scientific Opinion on nitrofurans and their metabolites in food

“…Nowadays, mostly macrocrystalline nitrofurantoin is used (see section 1.3.1) but there are still a few formulations that contain the microcrystalline form. Only in a few studies the particle size was specified (Conklin and Hailey, 1969;Borsa et al, 1976;Rosenberg and Bates, 1976;Männistö, 1978). Microcrystalline nitrofurantoin has a particle size smaller than 10 µm (Rosenberg and Bates, 1976;Conklin and Hailey, 1969), approximately 10 µm (Borsa et al, 1976) or 4-15 µm (Männistö, 1978).…”

“…Only in a few studies the particle size was specified (Conklin and Hailey, 1969;Borsa et al, 1976;Rosenberg and Bates, 1976;Männistö, 1978). Microcrystalline nitrofurantoin has a particle size smaller than 10 µm (Rosenberg and Bates, 1976;Conklin and Hailey, 1969), approximately 10 µm (Borsa et al, 1976) or 4-15 µm (Männistö, 1978). The reported particle sizes of macrocrystalline nitrofurantoin were: 75-180 µm (Conklin and Hailey, 1969;Rosenberg and Bates, 1976), 80-180 µm (Borsa et al, 1976) or 90-200 µm (Männistö, 1978).…”