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A Clinical Single-Pass Perfusion Investigation of the Dynamic in Vivo Secretory Response to a Dietary Meal in Human Proximal Small Intestine

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Purpose

To investigate the gastrointestinal secretory and enzymatic responses to a liquid meal during in vivo perfusion of the proximal human jejunum.

Methods

Human intestinal fluid was collected from the proximal jejunum by single-pass in vivo perfusion (Loc-I-Gut). The fluid was quantitatively collected at 10-min intervals during 90 min while perfusing a nutritional drink at 2 mL/min. Quantification of lipids in the fluid leaving the segment was performed by using novel chromatographic methods.

Results

The overall bile acid concentration varied between 0.5 and 8.6 mM with a peak level 40 min after the start of the liquid meal perfusion. The total concentration of phospholipids was between 0.1 and 3.9 mM and there was a rapid degradation of phosphatidylcholine to lysophosphatidylcholine. The tri-, di-, monoglycerides and free fatty acid levels increased sharply in the beginning and reached steady-state levels between 7 and 9.5 mM.

Conclusions

There is a rapid secretion of bile in response to food. Most of the dietary lipids are found in the form of their degradation products in vivo in human jejunum. This novel in vivo characterization, based on direct and high-recovery sampling of intestinal fluids, forms a basis for further development of improved in vitro drug dissolution test media.

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Abbreviations

AUC:

area under the concentration time curve

BCS:

biopharmaceutical classification system

C :

the concentration of the component found in the analyses

C in :

the concentration of the lipid components in the NuTRIflex entering the intestinal segment

C max :

maximum perfusate concentration

C out :

the mean steady-state concentration of the nutritional lipids analyzed in the sample of the perfusate leaving the intestinal segment

C out-comp :

the concentration of each NuTRIflex component in the intestinal fluid leaving the segment after compensation for dilution in the intestinal segment has been made

C t, in vivo :

the concentration of each component upon dilution in the small intestine in the time interval t

ELS:

evaporativelight scattering

HIF:

human intestinal fluid

HPLC:

high-performance liquid chromatography

L :

the length of the perfused jejunal segment (10cm)

LOQ :

limit of quantification

PEG :

polyethylene glycol

PEG in :

concentration of 14C-PEG 4000 (dpm/mL) en-tering the segment

PEG out :

concentration of 14C-PEG 4000 (dpm/ml) leaving the segment

NWF :

net water flux

SEM:

standard error of the mean

T max :

the time at which the maximum perfusate concentration occurred

Q in :

the flow rate (mL/min) of the perfusion solution entering the segment

Q out,t :

the flow rate of the perfusate leaving the segment during the time interval t

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Acknowledgments

We thank Dr. Christer Tannergen and Dr. Niclas Petri for assistance in the collection of intestinal fluid.

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Authors and Affiliations

  1. Department of Pharmacy, Uppsala University, Box 580, S-751 23, Uppsala, Sweden

    Eva M. Persson & Hans Lennernäs

  2. Department of DMPK and Bioanalytical Chemistry, AstraZeneca R&D, S-431 83, Mölndal, Sweden

    Ralf G. Nilsson, Göran I. Hansson & Lars J. Löfgren

  3. Department of Preformulation and Biopharmaceutics, AstraZeneca R&D, S-431 83, Mölndal, Sweden

    Fredrik Libäck & Bertil Abrahamsson

  4. Department of Surgery, University Hospital, S-751 85, Uppsala, Sweden

    Lars Knutson

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  1. Eva M. Persson
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Correspondence to Hans Lennernäs.

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Persson, E.M., Nilsson, R.G., Hansson, G.I. et al. A Clinical Single-Pass Perfusion Investigation of the Dynamic in Vivo Secretory Response to a Dietary Meal in Human Proximal Small Intestine. Pharm Res 23, 742–751 (2006). https://doi.org/10.1007/s11095-006-9607-z

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