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Abstract

Recently a new in vivo approach in man, using a regional intestinal perfusion technique, has been developed. The perfusion tube consists of a multichannel tube with two inflatable balloons, which are placed 10 cm apart. The tube is introduced orally and the time required for insertion and positioning of the tube is approximately 1 hr. In the present study eight healthy subjects were perfused in the proximal jejunum on three separate occasions. The first two perfusion experiments used the same flow rate, 3 ml/min, and the third experiment used 6 ml/min. Phenazone (antipyrine) was chosen as the model drug. The recovery of PEG 4000 in the outlet intestinal perfusate was complete in experiments 1 and 2, but slightly lower (90%) when the higher flow rate was used. The mean (+/- SD) fraction of phenazone absorbed calculated from perfusion data was 51 +/- 12% (3 ml/min), 64 +/- 19% (3 ml/min), and 42 +/- 27% (6 ml/min) for the three experiments, respectively. The mean fraction absorbed estimated by deconvolution of the plasma data was 47 +/- 16%, 51 +/- 19%, and 38 +/- 26%, respectively. The effective permeability of phenazone was 5.3 +/- 2.5, 11 +/- 6.8, and 11 +/- 12 (x 10(4) cm/sec, respectively. We have shown that it was possible to establish a tight intestinal segment which behaved as a well-mixed compartment. The low perfusion rate of 3 ml/min was preferred, since it resulted in the lowest variability in absorption.(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

“…When P eff is experimentally determined from absorption data (e.g. luminal disappearance rate of the drug), its value is scaled by the SA available in the test segment, usually assuming a cylindrical SA (13). This SA does not reflect all available structures in the SI that might increase the surface area compared to a cylinder, i.e.…”

“…In the double-balloon technique, the drug is single-pass perfused in solution to conscious human volunteers employing a multilumen tube. The reader is referred to the following references for more details about the clinical procedure, the data analysis and the doubleballoon technique (1,2,(13)(14)(15)(16).…”

Simultaneous quantification of the enantiomers of verapamil and its N-demethylated metabolite in human plasma using liquid chromatography–tandem mass spectrometry

“…Eight healthy male volunteers, aged 23-35 years and weighing 60-95 kg, gave their informed consent to participate in this in vivo intestinal perfusion study by using the Loc-I-Gut ® method [26,27]. All subjects underwent a full clinical examination prior to the study and all had normal clinical and laboratory values.…”

Simultaneous determination of naproxen, ketoprofen and phenol red in samples from rat intestinal permeability studies: HPLC method development and validation

“…The reproducibility of the data obtained using these techniques are reduced * Corresponding author. by several factors; therefore, new experimental techniques using a multichannel tube with two inflatable balloons have been developed [1][2][3][4]. In 1992, Lennernas et al evaluated the potential of the new perfusion technique as a tool for investigation of drug absorption mechanisms in the human intestine [3].…”

“…by several factors; therefore, new experimental techniques using a multichannel tube with two inflatable balloons have been developed [1][2][3][4]. In 1992, Lennernas et al evaluated the potential of the new perfusion technique as a tool for investigation of drug absorption mechanisms in the human intestine [3]. Moreover, a segmental steady-state perfusion technique has been carried out by Gramatte and Richter in 1993 using a triple lumen tube to investigate the site-specific absorption of paracetamol in human small intestine [5].…”