Абстрактный

Preclinical Pharmacokinetic Evaluation of Etoricoxib-Cyclodextrin-PVP Complexes

K. P. R. Chowdary and A. Seetha Devi

Etoricoxib, a relatively new widely prescribed NSAID drug belongs to class II under BCS and exhibit low and variable bioavailability due to its poor aqueous solubility and needs enhancement in dissolution rate and bioavailability to derive its maximum therapeutic efficacy. Cyclodextrin complexes exhibited rapid and higher dissolution of etoricoxib, when compared to etoricoxib pure drug. Addition of hydrophilic polymers such as PVP, HPMC and PEG has further enhanced the dissolution rate and efficiency of etoricoxib from CD complexes. The objective of the present study is to evaluate the pharmacokinetics and bioavailability of etoricoxib-C D-PVP complexes in comparison to etoricoxib in rabbits. Rapid & higher absorption and bioavailability of etoricoxib was observed, when administered as CD complexes. Addition of PVP has further enhanced th e rate and extent of absorption (bioavailability) of etoricoxib from Et- β CD and Et-HP β CD complexes. A 3.97, 7.93, 4.99 and 6.5 fold increase in the Ka was observed, respectively with Et- β CD (1 : 2), Et- β CD-PVP (1 : 2 : 0.3), Et-HP β CD (1 : 2) and Et-HP β CD- PVP (1 : 2 : 0.3) complexes, when compared to etoricoxib pure drug. A 1.84, 1.86, 1.63 and 1.91 fold increase in (AUC) 0 ∞ was observed, respectively with Et- β CD (1:2), Et- β CD-PVP (1 : 2 : 0.3), Et-HP β CD (1 : 2) and Et-HP β CD-PVP (1 : 2 : 0.3) complexes, when compared to etor icoxib pure drug. β CD and HP β CD have markedly enhanced both; the rate (K a ) and extent (AUC) of absorption (i.e. bioavailability) of etoricoxib. Addition of PVP has further enhanced both; the rate of absorption and extent of absorption of etoricoxib from Et- β CD and Et-HP β CD complexes. Hence, a combination of CDs and PVP is recommended for enhancing the bioavailability of etoricoxib, a BCS class II drug.