Technique perfusion

Here gaseous exchange, pH control and medium replenishment occur in a second vessel distinct from the cell growth chamber. From this vessel the medium is pumped into the growth chamber which may be a modified microscope slide, a roller bottle or a capillary bed etc. 

---

The CAT model considers passive absorption, saturable absorption, degradation, and transit in the human small intestine. However, the absorption and degradation kinetics are the only model parameters that need to be determined to estimate the fraction of dose absorbed and to simulate intestinal absorption kinetics. Degradation kinetics may be determined in vitro and absorption parameters can also be determined using human intestinal perfusion techniques [85] therefore, it may be feasible to predict intestinal absorption kinetics based on in vitro degradation and in vivo perfusion data. Nevertheless, considering the complexity of oral drug absorption, such a prediction is only an approximation. 

T. Salmonson, and G. Amidon. The effect of amiloride on the in vivo effective permeability of amoxicillin in human jejunum experience from a regional perfusion technique., Eur. J. Pharm. Sci. 2002, 15, 271-277... 

Fig. 7.4. The Loc-I-Cut perfusion technique for the proximal region of the human jejunum.

Methodological Aspects on in vivo Intestinal Perfusion Techniques... 

Methodological Aspects on In-vivo Intestinal Perfusion Techniques j 163... 

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-leucine and L-phenylalanine in human jejunum in vivo. P r were measured using a single-pass perfusion technique at concentrations of 2.5 mM, 6.7 mM, 40 mM and 0.06 mM for l-dopa, a-methyldopa, L-leucine and L-phenylalanine, respectively. 

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. 

Keywords Oral absorption Bioavailability Models of small intestine Intestinal permeability Intestinal perfusion techniques Intestinal versus hepatic first-pass metabolism... 

In general, the intestinal perfusion technique has proved a powerful research tool, despite these shortcomings. Its primary application has been in the estimation of Peft the model also lends itself to comparing permeability differences from one site to another along the intestine, an essential prerequisite for accurately classifying controlled release products [59]. Cross-over experiments tend... 

Lennernas s group at Uppsala has performed extensive studies to confirm the validity of this in vivo experimental set-up at assessing the rate and the extent of drug absorption. Recovery of PEG 4000 (a non-absorbable marker) is more than 95%, which indicates that the absorption barrier is intact. In addition, maintenance of functional viability of the mucosa during perfusion has been demonstrated by the rapid transmucosal transport of D-glucose and L-leucine. Estimation of absorption half-lives from the measured Pefr agree well with half-lives derived from oral dose studies in humans (i.e. physiologically realistic half-lives). Human Peff estimates are well correlated with the fraction absorbed in humans, and served as the basis for BCS development, and hence the technique is ultimately the benchmark by which other in situ intestinal perfusion techniques are compared. The model has been extensively used to... 

---