Investigation of Contributory Factors That Influence Zolpidem Metabolism in Vitro

Insomnia is an ongoing public health problem in the United States and many other countries. Zolpidem has been one of the most frequently prescribed sleep-inducing drugs to treat insomnia in the United states for the last 30 years. Although having relatively fewer side effects compared to the benzodiazepine-class hypnotics, zolpidem still has a possibility to be hazardous for some individuals, being cleared from the body differently in specific groups.;In the present study, we explored the possible contributory role of an individual's intrinsic and extrinsic factors in affecting the rate of zolpidem metabolism in vitro. We evaluated the metabolic data from 61 HLM preparations by measuring the production of three metabolites and establishing a metabolic data profile using HPLC method in vitro .;Of all the factors evaluated in present study, we found most interesting inter-racial/ethnic differences in zolpidem biotransformation in vitro . Black, white, and Hispanic racial/ethnic groups were investigated. Black groups showed the highest mean NMT production value, being 49% and 56% higher compared to the white and Hispanic groups, respectively. There were differences between black and white racial groups (p=0.004), and between black and Hispanic groups (p=0.0057). Both differences were statistically significant (p <0.05).;Although we found statistically significant differences among racial/ethnic groups, potential genetic causes such as CYP polymorphisms underlying those differences in the groups could not be explained in the present study. Once DNA is obtained from each of the 61 HLM preparations, we can perform genotyping analysis and can match it with metabolic data that was established in this study. These will help us to find out the plausible causes underlying the metabolite production differences in race/ethnic groups.