Jejunal perfusion approach

The jejunal perfusion approach generates data which may be used to predict absorption/bioavailability and to establish in vivo-in vitro correlation (IVIVC) even for extended release (ER) products. If a dmg is transported mainly by passive diffusion and has a jejunal Peff higher than metoprolol (1.5 x 10-4 cm s 1 = high-permeability compound), it can be expected to be completely absorbed throughout the small and large intestine [5, 46]. 

H Lennernas, O Ahrenstedt, R Hallgren, L Knutson, M Ryde, LK Paalzow. Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man. Pharm Res 9 1243-1251, 1992. 

A direct in vivo assessment was carried out with the single-pass perfusion approach in the human jejunum by using the Loc-I-Gut technique with R/S-verapamil (log D6 5 2.7, octanol/water pH 7.4 MW 455 Da) as the model compound for CYP 3A4 and P-gp-mediated local intestinal kinetics [2, 34, 35, 122] (see Figs. 7.7 and 7.9). The Peff for both enantiomers at each of the concentrations (4.0, 40, 120, and 400 mg L-1) was 2.5 x 10 4, 4.7 x 105.5 x 104 and 6.7 x 104 cm s-1, respectively (Fig. 7.15) [34, 35], A luminal concentration of 400 mg L 1 is expected to be achieved in the upper part of the small intestine after oral administration of a 100-mg dose of verapamil in an immediate-release dosage form [1, 34, 35], The three other perfusate concentrations represent fractions of the dose when 30%, 10%, and 1%, respectively are left to be absorbed [34, 35], The increased in vivo jejunal Peff of R/S-vcrapamil, along with its increased luminal perfusate concentration, is in accordance with a saturable efflux mechanism mediated by... 

Lennernas H, Ahrenstedt O, Hallgren R, Knutson L, Ryde M and Paalzow LK (1992) Regional Jejunal Perfusion, a New In vivo Approach to Study Oral-Drug Absorption in Man. Pharm Res 9 pp 1243-1251. 

---