Site-dependent small intestinal absorption of ranitidine

Abstract

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)

Translating Human Effective Jejunal Intestinal Permeability to Surface-Dependent Intrinsic Permeability: a Pragmatic Method for a More Mechanistic Prediction of Regional Oral Drug Absorption

“…Herein, the reported regional P eff,i values were re-calculated from the absorption data originally reported in the literature (44)(45)(46)(47)(48)(49). This was done in order to allow the incorporation of the different mSA calculation methods for the estimation of the regional P eff values; the details of the re-calculation procedure can be found in Section 3 the Supplementary Material.…”

“…For M2, the mSA available (Eq. 5) across the length of the test portion of the multiple lumen tube was employed (44)(45)(46)(47)(48)(49). This mSA was defined as the difference in cumulative mucosal surface area between the distal (x final,i ) and proximal (x initial,i ) collection orifices of the perfusion tube.…”

“…This mSA was defined as the difference in cumulative mucosal surface area between the distal (x final,i ) and proximal (x initial,i ) collection orifices of the perfusion tube. The positions required to calculate the mSA according to M2, x final,i and x initial,i , were assumed to be the same for all the experiments and were representative of the positions informed for the jejunal and ileal perfusion experiments (44)(45)(46)(47)(48)(49). This was done due to the high variability reported in the positioning of the test segments of the multiple lumen tube or the lack of information about it in some of the references.…”

“…The observed absorption clearance (CL abs, ileal(observed) ) was derived from the absorption data reported in the original references of the single-pass perfusion experiments (44)(45)(46)(47)(48)(49). This was calculated as per Eq.…”

Differential Substrate and Inhibitory Activities of Ranitidine and Famotidine toward Human Organic Cation Transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3)

“…Despite their hydrophilic nature, both ranitidine and famotidine are relatively well absorbed in humans and exhibit oral bioavailability of 40 to 70% (van Hecken et al, 1982;Yeh et al, 1987). They are primarily eliminated unchanged via renal excretion (ϳ70%) with minor contributions from hepatic metabolism (ϳ20 -30%) and intestinal secretion (Lin, 1991;Gramatte et al, 1994). Biliary excretion of ranitidine and famotidine is insignificant in both rats and humans (Klotz and Walker, 1990;Suttle and Brouwer, 1994).…”