Impact of body mass index, calculated blood volume, sex and age on observed alprazolam concentrations in urine
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Benzodiazepines (BZDs) were originally developed in the 1950s to treat anxiety and insomnia conditions.1,2 BZDs are classified as central nervous system (CNS) depressants as they produce sedative and hypnotic effects by acting on the central nervous system’s key inhibitory neurotransmitter, gamma-aminobutyric acid type A receptor (GABAA).3,4 Although commonly prescribed, they are still labeled as a schedule IV under the Controlled Substance Act.5,6 Like all other prescribed controlled substances, benzodiazepines have been misused; in some cases patients do not comply with the recommended doses and refuse to take the drug as often as necessary while in others they are abused. The primary goal of this research was to evaluate the quantitative and qualitative measurements of a population taking alprazolam based on defined parameters. The results were then analyzed to discuss trends and make comparisons about the effects of the parameters being monitored. Qualitative results include a known prescription for the drug, the presence of the drug and its metabolite as well as the sex of the individual. Quantitative results include calculated body volume (CBV) as it paralleled to BMI, patient age, drug dose, drug and metabolite concentration, and specimen validity testing (SVT) results. For the purpose of this study a data set consisting of a population prescribed alprazolam was provided by a therapeutic drug-testing lab. This lab utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to run a targeted analysis.7 The data analysis was conducted using R version 3.5.1 (R Foundation, Vienna, Austria). R is a statistical environment for computing and graphic production.8 To transform and normalize the concentration of alprazolam and it’s metabolite, alpha-hydroxyalprazolam, in urine samples a method was adopted that accounts height, weight, sex, prescribed drug dose and calculated parameters for each patient including BMI, lean body weight (LBW), body surface area (BSA) and CBV (Equation 1 and 2). 9 Age was later accounted for by separating the population into predetermined age groups. Results revealed that the population consisted of 53.8% more females than males, a common trend seen in the United States.2 The number of individuals with alprazolam prescriptions increased as age increased. More males between the ages of 19 and 49 were prescribed alprazolam than women of the same age: 30.8% and 28.7%, respectively. In the 70 years of age and older category, more females were prescribed alprazolam than males (16.2% and 13.2%, respectively). CBV for males was higher than females and this trend was consistent throughout age groups. The distribution characteristics of normalized alprazolam and alpha-hydroxyalprazolam most resembled that of a normal Gaussian distribution. The alprazolam range for males spanned from 20 ng/mL to 1719ng/mL while in females the range was between 20ng/mL and 1490ng/mL. When age was considered, the alprazolam concentration range was larger in females ages 40-49 and 70 years old and older. The alpha-hydroxyalprazolam concentrations were similar between females than males: 5-2484ng/mL and 20-2459ng/mL, respectively. This research illustrates that the study of individual BZDs can be used to highlight trends throughout a population specific to the drug of interest. While individuals differ in many factors of metabolism and drug distribution, this data can be utilized as a resource for evaluating commonly detected/seen concentration ranges.