الفهرس 
Gastrointestinal tract physiology and functionOnly 14 pages are availabe for public view
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Abstract
The Biopharmaceutics Classification System (BCS) of drugs has emerged
chiefly to afford a scientific approach for assorting oral drugs based on their
intestinal permeability and aqueous solubility. Medications that fit the BCS III
class possess a poor permeability profile; even though, they demonstrate the
desired pharmacological response in vitro. Therefore, these molecules exhibit
defiance when formulated into oral dosage forms due to permeability-related
issues. Several approaches have been explored with an aim to tackle this issue
without compromising solubilities such as permeation enhancers, ion-pairing,
prodrugs, and nanotechnology-based approaches. Linagliptin is a class III new
potent oral anti-diabetic drug that exerts its action by inhibiting the dipeptidyl
peptidase-4 (DPP-4) enzyme, thus extending the duration of GLP-1 and GIP
which in turn controls postprandial glucose. Linagliptin is reported to have a
limited bioavailability after oral administration which is about 29.5%. The
most reasonable explanation is that P-glycoprotein (P-gp) efflux transporters
restrict its absorption in addition to the inherited moderate permeability of the
drug itself. For these reasons, linagliptin plasma concentration and its antidiabetic behavior could be altered when it is co-administered with other P-gp
enzyme inhibitors including drugs with reported P-gp modulatory action or
excipients that cause a membrane perturbation which may also disturb the
function of the membrane-bound proteins such as P-gp; consequently, these
P a g e | 2
Pharmaceutical Technology Department, College of Pharmacy, University of Tanta, Tanta, Egypt
excipients can boost linagliptin absorption by increasing its permeability
without being moved back to the intestinal milieu.
Hence, the prime purpose of this research isto study the potential of altered
absorption of linagliptin when it is simultaneously perfused with carvedilol,
atorvastatin, or sodium cholate. Jejunal and ileal segments were utilized for
this examination regarding the maximal P-gp efflux transporters expression in
these segments. To do this, initially, linagliptin membrane transport properties
from several gastrointestinal anatomical sites, including the possibility of
saturable drug influx, were investigated. For these objectives, in situ singlepass intestinal perfusion technique was applied, adopting the rabbit as an
animal model.
The proceeding sections summarize the studies performed to achieve this
purpose.