Loc-I-Gut® technique

Fig. 7.10. Correlation between in vivo Peff (determined with the Loc-I-Gut technique in humans) and octanol/buffer (pH 6.5) distribution coefficients for several common drugs. Drugs with octanol/buffer (pH 6.5) distribution coefficients >0 are highly permeable and well absorbed in humans (fa > 90%).

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... 

Fig. 7.7. Human in vivo permeability values (Peff) can be determined using a single-pass perfusion technique (Loc-I-Gut) in humans. These human Peff values correlated very well...

L. BonlOkke, L. Hovgaard, H. G. Kristensen, L. Knutson, H. Lennernas. Direct estimation of the in vivo dissolution of spironolactone, in two particle size ranges, using the single-pass perfusion technique (Loc-I-Gut ) in humans. Ear. J. Pharm. Sci. 2001, 12, 239-250. 

Figure 9.4 Loc-I-Gut is a perfusion technique for the proximal region of the human jejunum. The multichannel tube is 175 cm long and is made of polyvinyl chloride with an external diameter of 5.3 mm. It contains six channels and is provided distally with two 40 mm long, elongated latex balloons, placed 10cm apart, each separately connected to one of the smaller channels. The two wider channels in the center of the tube are for infusion and aspiration of perfusate. The two...

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