The effect of crystal size, gastric content and emptying rate on the absorption of nitrofurantoin in healthy human volunteers.

The effect of four crystal sizes, gastric contents, and gastrointestinal motility on the absorption and excretion of nitrofurantoin was studied in three separate cross-over studies on 10 healthy volunteers. Microcrystal preparation gave an early and high serum peak. The greater the crystal size was, the smaller was the peak serum concentration. Correspondingly, microcrystal preparations gave initially very high nitrofurantoin concentrations in urine. Macrocrystal preparation had a not significantly longer excretion time than the other preparations. Food did not increase the serum nitrofurantoin concentrations, but excretion during 4 to 6 h was considerably greater than after fasting. In contrast, antacid and the use of a delayed-release preparation greatly worsened the biovailability of nitrofurantoin. An increased gastric emptying rate induced by metoclopramide significantly worsened the absorption of nitrofurantoin, but atropine only retarded the absorption and the principal excretion in urine occurred during 4 to 8 h.