Data analysis on effects of therapeutic drug monitoring, dosing, and age on observed meprobamate concentrations in urine samples
Iarussi, Paul J.
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Prior to the development of benzodiazepines (BZDs) in the 1950’s, a class of drugs known as tranquilizers were used in psychiatry to treat patients experiencing anxiety and fear as well as more challenging states of psychosis such as schizophrenia. The first minor tranquilizer and anxiolytic compound that was widely used in the United States and much of the world was meprobamate in the 1950s. Meprobamate is a carbamate compound typically administered in tablet form and ingested orally as its route of administration. Meprobamate is also the major metabolite of the drug carisoprodol, which is sold under the brand name Soma ®. Both meprobamate and carisoprodol are schedule IV substances under the Controlled Substance Act as there is reported abuse with each substance. The primary goal of this research is to determine whether collected patient data reflects appropriate usage of their carisoprodol prescription in treatment of anxiety and if urine drug testing (UDT) and specimen validity testing (SVT) can support or refute the effectiveness of a patient’s treatment by measuring resulting meprobamate concentration. For the purpose of this study, a data set consisting of a population that was prescribed carisoprodol was provided by a therapeutic drug-testing lab. Qualitative results include a known prescription for carisoprodol, the presence of carisoprodol as well as the main anxiolytic metabolite meprobamate, whether a patient’s sample passed or failed SVT, and the sex of the individual. Quantitative results include initial and reported drug dosage, target analyte concentration, age, SVT result and body mass index (BMI). The lab used liquid chromatography tandem mass spectrometry (LC-MS/MS) to run analysis of urine specimen. Data analysis was conducted using R Studio version 3.5.1 (R Foundation, Vienna, Austria). R Studio is a statistical program that is utilized for computation and production of graphics. Statistical analysis and sub setting was used to find relationships and trends of meprobamate concentrations as they relate to age, BMI, dosage and SVT parameters. In this study of 1,672 patients, 1,067 were female and 685 males with females having 63.8% of the patient population. Of the overall population, 33.3% had a carisoprodol dose between 700-1050 mg, equivalent to 2 to 3 doses of 350 mg, in tablet form daily. 70.5% of the patient population was deemed overweight in terms of BMI yet had a lower average meprobamate concentration in urine compared to normal weight patients. The majority of participants in the study, 82.5% of females and 84.3% of males, who had a prescription for carisoprodol were between the ages of 40 and 69. SVT testing parameters were used to filter patient data a second time. Certain samples fell outside of accepted ranges for pH, creatinine and specific gravity. Of all 1,672 submitted samples, 18.2% failed at least one parameter or contained an illicit substance. The average meprobamate concentration for males was 26,896 ng/mL (530-292,133 ng/mL range) and the average concentration for females was 28,802 ng/mL (500 to 336,853 ng/mL range). This research highlights the need for compliance drug testing to ensure that patients are taking their prescribed dose appropriately and monitoring for signs of abuse. The trends discovered in this research can be used to evaluate known carisoprodol dosing and relate it to meprobamate concentration in urine drug testing. There are likely to be variations in patients’ metabolism and overall health but having a sense of how much carisoprodol to prescribe to individuals based on previous data will be effective for treatment of anxiety.