The site-dependent, small intestinal absorption characteristics of ranitidine were estimated by the intestinal steady state perfusion technique (triple lumen tubing system) combined with simultaneous measurement of serum concentrations of ranitidine. Ranitidine 150 mg.l-1 was perfused at 10 ml.min-1 for 180 min in different sites of the small intestine between 65-250 cm beyond the teeth. Each of 9 healthy, male volunteers was examined twice, using perfusion sites in different regions of the small intestine to permit intraindividual comparisons. The absorption rates (micrograms.30 cm-1.min-1) calculated from intestinal samples showed distinct site-dependence; the highest rates (medians 160-923 micrograms.30 cm-1.min-1) were found in the most proximal region (duodenojejunal junction), and the most distal perfusion sites (distal jejunum/ileum) showed median rates from 193 to 265 micrograms.30 cm-1.min-1. In both of these regions there was a significant positive correlation between the net intestinal water flux and the movement of ranitidine. Within the mid-jejunum, every subject showed marked secretion of ranitidine into the gut lumen (medians -338 to -124 micrograms.30 cm-1.min-1), and in this region there was no influence of water flux on ranitidine movement. The intraluminal results were confirmed by the corresponding site-dependent areas under the serum concentration-time curves (AUC), which decreased with the distance of the perfusion site from the teeth. After the more distal perfusions individual AUCs amounted to 64-16% of the AUCs obtained after more proximal applications. The results demonstrate the small intestine as the site of a gradient of absorption of ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides have rightly remained a cost-effective anti-microbial strategy for the treatment of gram-positive infections for some 25 years. However, in recent years there has been a review of the traditional thrice-daily administration regimen in favor of an extended dosing interval strategy that takes into account the individual patient's renal function. The general recommendations that have been provided to date have been adopted in various ways internationally. These approaches were a matter of discussion for the Clinical Pharmacokinetics Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology at its congress (Vancouver, Canada; November 1997), and will again be a workshop issue at the Cairns (Australia) congress of the Association (September 1999). The present report provides examples of how these practices have been applied at a group of centers from Canada (2 centers), The Netherlands, Egypt, and Australia. These reports demonstrate a variety of approaches and highlight the need for further research for assessing clinical outcomes from different dosing strategies.

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