The complexation of warfarin (W) enantiomers by a hydrosoluble high-molecular-weight beta-cyclodextrin/epichlohydrin polymer (EP/beta-CD polymer) was studied using HPLC with a mobile phase of methanol/0.1 M Na acetate/acetic acid (pH 4) at 22 degrees C. It was found that the complexes (W/beta-CD unit) have a 1:1 stoichiometry. The stability constants of the complex involving each enantiomer and the polymer beta-CD units were determined in the mobile phase, and the highest stability of the complex (S-warfarin/beta-CD unit) was observed. From the chromatographic separations of warfarin enantiomers on different beta-CD or its derivative supports, we have deduced the role of the simultaneous presence of several glyceryl (-O-CH(2)-CHOH-CH(2)-O-) and dihydroxypropyl (-O-CH(2)-CHOH-CH(2)OH) groups on one beta-CD ring in promoting the chiral recognition of warfarin enantiomers.
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http://dx.doi.org/10.1016/s0165-022x(02)00125-2 | DOI Listing |
Chirality
May 2024
Department of Physical Chemistry, Institute of Chemistry Campinas State University (UNICAMP), Campinas, SP, Brazil.
This study describes the interaction of human serum albumin (HSA) with the binol derivative (R)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol (R-BrB), which has its optical activity based on the prohibitive energetic barrier for conversion into the enantiomer (S)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol (S-BrB). The objective was to assess the ability of HSA to differentiate axial enantiomers based on their binding efficiency and their impact on the CD spectra. We discovered that both enantiomers were effective ligands, and the CD signal disappeared when equimolar amounts of R-BrB and S-BrB were simultaneously added, indicating no preference for either enantiomer.
View Article and Find Full Text PDFJ Pharm Bioallied Sci
March 2024
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jawa Barat, Indonesia.
Context: Warfarin is extensively used for venous thromboembolism and other coagulopathies. In clinical settings, warfarin is administered as a mixture of S-warfarin and R-warfarin, and both enantiomers are metabolized by multiple cytochrome P450 enzymes into many hydroxylation metabolites. Validation of analysis method and estimation of warfarin plasma levels are important, especially in narrow-index drugs such as warfarin.
View Article and Find Full Text PDFAnal Chem
April 2024
China Pharmaceutical University, Nanjing 210009, China.
Herein, a novel strategy was implemented to modulate the supramolecular interaction between enantiomers and chiral recognition sites (CRSs), effectively resolving the issue of CRS saturation. Randomly methylated-β-cyclodextrin (Rm-β-CD) was used as the CRS (host molecule), and polymerized ionic liquids [poly([vbim]TFSI)] were used as the supramolecular modulator (guest molecule), which self-assembled to generate thermosensitive supramolecular host/guest complexes. The enantiomeric binding capacity and enantioselectivity of chiral separation systems centered on supramolecular host-guest complexes are characterized by a high degree of temperature dependence.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
May 2024
Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China.
Warfarin is a widely used anticoagulant, and its S-enantiomer has higher potency compared to the R-enantiomer. S-warfarin is mainly metabolized by cytochrome P450 (CYP) 2C9, and its pharmacological target is vitamin K epoxide reductase complex subunit 1 (VKORC1). Both CYP2C9 and VKORC1 have genetic polymorphisms, leading to large variations in the pharmacokinetics (PKs) and pharmacodynamics (PDs) of warfarin in the population.
View Article and Find Full Text PDFBMC Complement Med Ther
February 2024
Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University, The Heilongjiang Key Laboratory of Drug Research, Harbin, 150086, P.R. China.
Background: Herb-drug interactions may result in increased adverse drug reactions or diminished drug efficacy, especially for drugs with a narrow therapeutic index such as warfarin. The current study investigates the effects of sodium ferulate for injection (SFI) on anticoagulation of warfarin from aspects of pharmacodynamics and pharmacokinetics in rats and predicts the risk of the combination use.
Methods: Rats were randomly divided into different groups and administered single- or multiple-dose of warfarin (0.
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