caa a22 4500 477128351 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19971101xx s 000 0 eng 10.1023/A:1012174217220 doi (NATIONALLICENCE)springer-10.1023/A:1012174217220 Absorption of D-Glucose in the Rat Studied Using In Situ Intestinal Perfusion: A Permeability-Index Approach [Elektronische Daten] [Yanfeng Wang, Renee Aum, Francis Tse] Purpose. A permeability-index approach was developed and used to study the transport of D-glucose in the jejunum and ileum of rats. Methods. The effective permeability coefficient (Pe) of [3H]D-glucose and [14C]antipyrine (an internal standard) in jejunum and ileum of four rats was determined using an in situ rat intestinal perfusion technique. The permeability ratio of the test compound (D-glucose) to the internal standard was defined as the permeability-index (Pi), which was mathematically independent of the length and surface area of the intestinal segment perfused. Using this approach, the transport of [3H]D-glucose in jejunum and ileum of eight animals was investigated at concentrations ranging from 1 to 300 mM. The tissue/perfusate distribution of [3H]D-glucose and [14C]antipyrine at steady state was also determined. Results. The variability (%CV) in Pi of D-glucose was only ∼5%, compared with 23−36% in Pe values of D-glucose or antipyrine alone. The permeability and tissue distribution of [14C]antipyrine were unaffected by the presence of D-glucose. In contrast, the permeability and tissue distribution of [3H] D-glucose were concentration-dependent in both jejunum and ileum. The transport of D-glucose was studied assuming that the transport was mediated by a carrier (with maximum flux, Vmax and dissociation constant, Km) as well as by non-saturable transport (Pd). The maximum transport capacity for D-glucose in jejunum (0.522 μmole/min/cm2) was twice that in ileum (0.199 μmole/min/ cm2), but the affinity (l/Km) was less than half of that in ileum (l/ (48.2 μmole/mL) vs. 1/(21.4 μmole/mL)), rendering a similar active transport efficiency (Vmax/Km) in these two regions. The non-saturable permeability (Pd) in jejunum (44.6 × 10−4 cm/min) was approximately twice that in ileum (20.4 × 10−4 cm/min). Conclusions. The permeability-index approach yielded parameters with reduced variability by eliminating potential imprecisions in length and surface area measurements of the intestinal segment perfused. D-glucose was transported via carrier-mediated systems in both jejunum and ileum, with different transport capacity and affinity in these two regions. Plenum Publishing Corporation, 1997 glucose nationallicence antipyrine nationallicence permeability nationallicence intestinal perfusion nationallicence rat nationallicence Wang Yanfeng Drug Metabolism and Pharmacokinetics Department, Novartis Pharmaceuticals Corporation, 07936, East Hanover, New Jersey aut Aum Renee Drug Metabolism and Pharmacokinetics Department, Novartis Pharmaceuticals Corporation, 07936, East Hanover, New Jersey aut Tse Francis Drug Metabolism and Pharmacokinetics Department, Novartis Pharmaceuticals Corporation, 07936, East Hanover, New Jersey aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1563-1567 0724-8741 14:11<1563 1997 14 11095 https://doi.org/10.1023/A:1012174217220 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012174217220 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Yanfeng Drug Metabolism and Pharmacokinetics Department, Novartis Pharmaceuticals Corporation, 07936, East Hanover, New Jersey aut NATIONALLICENCE 700 1- Aum Renee Drug Metabolism and Pharmacokinetics Department, Novartis Pharmaceuticals Corporation, 07936, East Hanover, New Jersey aut NATIONALLICENCE 700 1- Tse Francis Drug Metabolism and Pharmacokinetics Department, Novartis Pharmaceuticals Corporation, 07936, East Hanover, New Jersey aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1563-1567 0724-8741 14:11<1563 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer