Investigation of contributory factors that influence zolpidem metabolism in vitro
Park, Yummi.
2017
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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 ind... read moreividuals, 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 - ID:
- bg257s12z
- Component ID:
- tufts:22757
- To Cite:
- DCA Citation Guide EndNote
