Abstract
The sex-based differences between the effects of two novel sugar-based drug candidates, a sulfated polymannuroguluronate (SPMG-911) and an acidic oligosaccharide sugar chain compound (AOSC-971), on the enzymes CYP 1A2 and CYP 2E1 were investigated. The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP1A2, while AOSC-971 induced the CYP 2E1 in male rats. The results are useful for their safety evaluation, as well as for the prediction of inter-drug interactions associated with the two drugs.
Highlights
Sulfated polymannuroguluronate SPMG-911, a novel sulfated polysaccharide rich in 1-4 linked βD-mannuronate, prepared by sulfate modification of an alginate extract from brown algae, possesses a certain 1,4-linked β-D-mannuronate to α-L-guluronate ratio and an average molecular weight of 10KD
This study was related to a safety assessment of SPMG-911 and AOSC-971, as well as the prediction of interdrug interactions associated with them by investigating their influences on CYP 1A2 and CYP 2E1 enzymes, especially their sex-based differences, through comparison of pharmacokinetics data of caffeine and chlorzoxazone, which are the special “cocktail” probe drugs for CYP 1A2 and CYP 2E1, respectively [1, 2]
Rats in each group were injected with the caffeine and chlorzoxazone probe drugs and the concentrations of the samples were determined using the methodology described in the Experimental section
Summary
Sulfated polymannuroguluronate SPMG-911, a novel sulfated polysaccharide rich in 1-4 linked βD-mannuronate, prepared by sulfate modification of an alginate extract from brown algae, possesses a certain 1,4-linked β-D-mannuronate to α-L-guluronate ratio and an average molecular weight of 10KD. The acidic oligosaccharide sugar chain compound AOSC-971, a novel marine-derived acidic oligosaccharide, was extracted from brown algae Echlonia Kurome Okam by enzymatic. With an average molecular weight at 1300 Da., its primary sequence is rich in β-Dmannurinic acid linked by 1-4 bonds endowing the structure with a negative charge. This study was related to a safety assessment of SPMG-911 and AOSC-971, as well as the prediction of interdrug interactions associated with them by investigating their influences on CYP 1A2 and CYP 2E1 enzymes, especially their sex-based differences, through comparison of pharmacokinetics data of caffeine and chlorzoxazone, which are the special “cocktail” probe drugs for CYP 1A2 and CYP 2E1, respectively [1, 2]
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