Pharmacokinetic study of a novel anticancer drug DHDK in liver microsomes
Objective To conduct in vitro metabolic investigations of DHDK[(1E,4E)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one],a newly developed anticancer compound,and interspecies variation to corroborate its preclinical investigations.Methods In vitro metabolic stability and enzyme kinetics study of DHDK were carried out in rat and human liver microsomes of various species,using a stablished and validated HPLC method to quantify DHDK.The study also extrapolated to in vivo intrinsic hepatic clearance(CLh)in tandem with hepatic extraction ratio(ER)based upon in vitro data.Results The in vitro metabolic stability and kinetic differences were observed with insignificant difference between rat and human(P＞0.05).There were significantly lower CLh in vivo in human compared to rat(P＜0.05).Conclusion The metabolism study of DHDK shows moderate eliminated rates in vitro by both human and rat,dependent on cytochrome P450 metabolic enzymes and the cofactor nicotinamide adenine dinucleotide phosphate.
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