Kinetics of piretanide absorption from the gastrointestinal tract

In a recent report, it was shown that the loop diuretic piretanide is rapidly absorbed after placement of a piretanide solution in the duodenum, while the rate of absorption is definitely slower when the drug is instilled into the ascending colon (5). When piretanide is instilled into the stomach, the absorption process does not differ significantly from that after placement in the duodenum, neither with respect to amount nor rate (5). However, it was not clear from this study whether piretanide is directly absorbed from the stomach or rapidly released into the duodenum. In a study with five volunteers piretanide was instilled into the stomach via a gastroscope. The volunteers took part in two trial phases in a randomized cross-over design: in one phase the administration of 6 mg piretanide was preceded by intravenous administration of 40 mg hyoscine-N-butylbromide (HNB) to immobilize the stomach while in the alternative phase this coadministration of HNB was omitted. Furthermore, the volunteers were lying on their left side to avoid the gastric fluid leaking out into the intestine by gravity. From the concentration-time-curves monitored it can be concluded that piretanide is absorbed directly from the stomach for almost all subjects but with different rates. The rate of absorption increases clearly when the immobilizing effect of HNB disappears. It is most probable that returning peristaltic waves and succeeding gastric emptying results in enhanced absorption from the upper intestinal tract. Furthermore, a pharmacokinetic model which takes into account the differences in the rate of absorption along the gastrointestinal tract was adjusted to the data.(ABSTRACT TRUNCATED AT 250 WORDS)