چکیده (انگلیسی):

Purpose: Furosemide is a commonly used diuretic which is used in the treatment of
edema, congestive heart failure, hypertension and renal failure. Its absorption exhibits inter- and
intra-subject variability that can be attributed to many factors including the intestinal efflux pumps
such as the P-glycoprotein (P-gp). This study was done due to the great disagreement between what
is published in the literature regarding the influence of P-gp on furosemide and at the same time due
to the importance of this drug in the treatment of different conditions as described above. In addition,
an investigation of the effect of two of the commonly used pharmaceutical excipients
(hydroxypropyl b-cyclodextrin [HPbCD] and Tween 80) and also a P-gp inhibitor (verapamil
hydrochloride) on the intestinal absorption of this drug were also done.
Methods: The study utilized the everted intestinal sacs technique to investigate both the effect of
the efflux transporter (P-gp) on furosemide absorption and also the effect of the chosen excipients.
Results: The absorption of furosemide was significantly influenced by the P-gp as confirmed by the
everted vis the non-everted sacs together with the verapamil study in which the transport of furosemide
was inhibited by verapamil. In addition, Tween 80 was also shown to inhibit the P-gp pump
whereas the HPbCD did not significantly influence the efflux of furosemide in this study.
Conclusions: P-glycoprotein and some of the used excipients in the formulation play a very important
role in the transport of furosemide and other drugs. Thus excipients that affect the activity of
P-gp should be avoided when formulating drugs that are substrate for the P-gp or other efflux
pumps.