Abstract:
Background: Paclitaxel-induced neuropathy still remains a clinical problem
for patients undergoing chemotherapy. Objective: The objective of the
study was to determine the interaction between xylopic acid and pregab-
alinco-administration as well as their toxicity in paclitaxel-induced neuropa-
thy. Materials and Methods: Neuropathic pain was induced in rats with 2
mg/kg of paclitaxel on four alternate days (days 0, 2, 4 and 6). Equi effective
doses of xylopic acid and pregabalin that produced 50% anti-nociception
(ED50) were determined from their log-dose response curves in the cold
allodynia and thermal pain tests. Xylopic acid and pregabalin were again ad-
ministered to rats in a fixed ratio combination (1:1) of their ED50’s in order to
determine the experimental ED50 (Zexp) of the co-administered compounds.
Isobolograms were constructed to compare the Zexp to a theoretical ED50
(Zadd). Blood samples from the various treatment groups of rats were col-
lected for toxicological assessment of the co-administered compounds.
Results: The Zexp lay below the Zadd on the isobologram of the cold allodnia
test. The co-administration exhibited additivity in the thermal pain test. The
co-administration did not produce significant (p>0.05) toxicity in rats. The
co-administration may be beneficial in paclitaxel-induced neuropathy.