Loc-I-GUT

Fig. 7.3. The total Loc-I-Gut concept. Left a perfusion system of the duodenal segment. Center a tube system with double balloons which allow a segmental single-pass perfusion of jejunum. Right a perfusion system of the small intestinal stomi.

Fig. 7.6. a-c. Human in vivo permeabilities (Loc-I-Gut ) (see Fig. 7.4). The major are a cornerstone of the BCS the correlation of advantage of using Peff is that it can be fraction dose absorbed and permeability with measured irrespective of transport mecha-...

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...

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... 

A residence-time distribution analysis of the hydrodynamics within the intestine in man during a regional single-pass perfusion with Loc-I-Gut in-vivo permeability estimation, J. Pharm. Pharmacol. 1997, 49, 682-686. 

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 2.10 The Loc-I-Gut instrument allowing segmental intestinal perfusion in humans. The balloons are filled with air when the proximal balloon has passed the ligament of Treitz. The six-channel tube facilitates infusion of drug and marker, aspiration of perfusate and gastric drainage, and inflation of the two balloons [60].

Lennernas H, Lee I, Fagerholm U and Amidon GL (1997) A Residence-Time Distribution Analysis of the Hydrodynamics Within the Intestine in Man During a Regional Single-Pass Perfusion With Loc-I-Gut In-Vivo Permeability Estimation. J Pharm Pharmacol 49 pp 682-686. 

Correlation of in vitro data with human Pefjand Fa% was undertaken with a number of models [25, 27]. Although Fa% data is useful and more broadly available, the introduction of the Loc-I-Gut model by Lennernas allowed direct measurement of PefF. In the Loc-I-Gut model, a segment of the small intestine in humans is isolated using a balloon catheter, disappearance of the drug is measured and the Pgfr can be generated [40]. 

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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