Modulation of the Activity of Human Plasma Esterases by Binary and Ternary Mixtures of Water Miscible Organic Solvents During in Vitro Drug Metabolism Studies
INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES(2023)
Bombay Coll Pharm
Abstract
Organic solvents are commonly used in in vitro drug metabolism studies as co-solvents for lipophilic substrate/ new chemical entities. The effects of 1 % v/v final concentration of individual, binary and ternary mixtures of methanol, acetonitrile and dimethyl sulfoxide on human plasma esterases were investigated. The hydrolysis of p-nitrophenyl acetate to p-nitrophenol was monitored by ultraviolet spectrophotometry to follow esterase activity. Results indicated that the mixtures always showed less inhibition of esterase as compared to theoretically calculated additive inhibition based on individual solvent data. Results also indicated that dimethyl sulfoxide was the most-inhibitory solvent (59-64 % inhibition at 1 % v/v final concentration in incubation) and mixtures containing the least concentration of dimethyl sulfoxide caused the least inhibition of human plasma esterases.
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Key words
Binary solvents mixtures,ternary solvent mixtures,human plasma esterases
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