Clinical bioavaiability of nitrofurantoin--a case of bioinequivalence

In a crossover study of the bioavailability of marketed nitrofurantoin tablets, there were significant differences in the urinary excretion of nitrofurantoin suggestive of bioavailability problems with this drug. Standard in vitro assessments of dissolution rate and disintegration time were not correlated with bioavailability and failed to detect 3 to 18 fold differences in the amount of nitrofurantoin absorbed. In fact, four lots, made by the same manufacturer had almost identical in vitro measurements (dissolution rate; distinegration time), yet two of these lots were only 6.6 and 26% as available as the reference nitrofurantoin product, and two others were comparatively available. The need for the development of an in vitro - in vivo correlation for control of lot to lot uniformity has clearly been demonstrated for nitrofurantoin. Such correlations must include tests other than those presently required.