Abstract
Purpose: The aim of the present study was
investigating the effects of three anti-inflammatory drugs, on Sirolimus
protein biding. The binding site of Sirolimus on human serum albumin (HSA) was
also determined.
Methods: Six different
concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C.
Ultrafiltration method was used for separating free drug; then free drug
concentrations were measured by HPLC. Finally, Sirolimus protein binding
parameters was calculated using Scatchard plots. The same processes were
conducted in the presence of NSAIDs at lower concentration of albumin and
different pH conditions. To characterize the binding site of Sirolimus on
albumin, the free concentration of warfarin sodium and Diazepam, site I and II
specific probes, bound to albumin were measured upon the addition of increasing
Sirolimus concentrations.
Results: Based
on the obtained results presence of Diclofenac, Piroxicam and Naproxen, could
significantly decrease the percentage of Sirolimus protein binding. The Binding
reduction was the most in the presence of Piroxicam. Sirolimus-NSAIDs
interactions were increased in higher pH values and also in lower albumin
concentrations. Probe displacement study showed that Sirolimus may mainly bind
to site I on albumin molecule.
Conclusion: More considerations in co-administration of NSAIDs
and Sirolimus is recommended.