Investigation of contributory factors that influence zolpidem metabolism in vitro
Abstract: 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 ... read moreindividuals, 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.
Thesis (M.S.)--Tufts University, 2017.
Submitted to the Dept. of Pharmacology & Experimental Therapeutics.
Advisor: David Greenblatt.
Keywords: Pharmacology, and Medicine.read less