Studies on potential interaction between cinacalcet hydrochloride and diclofenac sodium

Cinacalcet (CT) is an important drug for the treatment hyperparathyroidism. Only few studies havereported thepotential interaction between CT and other potentially coadministered drugs. In this study, the potential of invitro interaction between CT and DF sodium (DF-Na) was investigated. An ion pair...

Full description

Saved in:
Bibliographic Details
Published in:Biophysical chemistry 2020-11, Vol.266, p.106460-106460, Article 106460
Main Authors: Hamdan, Imad I., El-Sabawi, Dina, Tverdokhleb, N.M., Lantushenko, A.O., Evstigneev, M.P., Abu-Dahab, Rana
Format: Article
Language:English
Subjects:
Cinacalcet
Diclofenac
Drug interaction
Ion pair
Molecular structure
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cinacalcet (CT) is an important drug for the treatment hyperparathyroidism. Only few studies havereported thepotential interaction between CT and other potentially coadministered drugs. In this study, the potential of invitro interaction between CT and DF sodium (DF-Na) was investigated. An ion pair salt of CT with DF was obtained by mixing the two compounds in solution; the product was fully characterized by HPLC analysis, UV, FTIR, NMR spectroscopy in addition to DSC. The solubility and partition coefficients were found to significantly decrease and increase, respectively, for the obtained ion pair salt in comparison to the parent compounds. Dissolution studies in phosphate buffer pH 6.8 revealed a significant decrease in the dissolution of an already poorly water soluble drug (decrease to ~20% of the original). Permeation studies, through Caco-2 cells monolayer, revealed a significant decrease in permeation of CT when coexisted with DF (almost to half). Apparent permeability coefficient (Papp) decreased from 3.6 × 10−6 to 1.8 × 10−6 cm/s. Interestingly, a structure for the formed CT-DF salt that could explain the above findings (increase in lipophilicity), could be proposed based on structural modelling, molecular dynamic simulations and NMR proton chemical shifts analysis. [Display omitted] •Diclofenac interacts with cinacalcet by ion pair formation.•Diclofenac-cinacalcet ion pair has a significantly lower solubility.•Diclofenac influences the absorption of cinacalcet through Caco-2 cells.•NMR modelling enabled details of molecular arrangements of the ion pair.
ISSN:0301-4622
1873-4200
DOI:10.1016/j.bpc.2020.106460