Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man.
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)
Lennernäs
H
H
Department of Biopharmaceutics and Pharmacokinetics, University of Uppsala, Sweden.
Ahrenstedt
O
O
Hällgren
R
R
Knutson
L
L
Ryde
M
M
Paalzow
L K
LK
D000328:Adult; D000983:Antipyrine / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007441:Intubation, Gastrointestinal; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism; D009994:Osmolar Concentration; D010477:Perfusion; D013056:Spectrophotometry, Ultraviolet; D014882:Water-Electrolyte Balance / Q000502:physiology
D005947:Glucose; D000983:Antipyrine