Barsaklardan Paraselüler Ilaç Absorpsiyonu Üzerine Permeabilite Artırıcı Ajanların Etkisinin Araştırılması
Özet
The aim of this study was to investigate the effect of permeability enhancers on
paracellular drug absorption. For this purpose, acyclovir classified as Class III drug
(high solubility and low permeability) according to Biopharmaceutics Classification
System and transported via paracellular pathway with passive diffusion was used as
the model compound. Effect of excipients with polymer and surfactant properties
(chitosan, dimethyl β-cyclodextrin, sodium caprate, sodium lauryl sulphate) on the
absorption and permeability of acyclovir across different rat intestinal segments
(jejunum, ileum and colon) was investigated using in situ intestinal perfusion studies.
Initially, all segments were perfused simultaneously with acyclovir containing
perfusion medium, and then perfused with acyclovir and permeability enhancer
containing perfusion medium. Metoprolol and phenol red were added as the
reference compounds to all perfusion mediums. Acyclovir, metoprolol and phenol
red amounts in the samples were determined by means of a validated HPLC method.
The results obtained from the perfusion studies indicated that sodium caprate has the
highest permeability enhancing effect. Sodium caprate increased the permeability
values of acyclovir 6.71-fold im jejunum, 6.83-fold in ileum and 4.14-fold in colon.
Dimethlyl β-cyclodextrin has not demonstrated permeability enhancing effect on the
selected model compound (acyclovir). On the other hand, although chitosan and
sodium lauryl sulphate have permeability enhancing effect this effect was statiscally
significant only in the jejunum (p=0.043). Even though, increase in permeation was
observed in jejunum and colon, this increase was not significant (p>0.05). The
results obtained from this study indicate that permeation enhancing agents can be
effective in increasing bioavailability of compounds with low absorption and
absorbed via paracellular route.
