Evaluating the Relationship Between Carisoprodol Concentrations and Meprobamate Formation and Inter-Subject and Intra-Subject Variability in Urinary Excretion Data of Pain Patients

Abstract

Using urinary carisoprodol data from pain patients, our objectives were to determine the relationship between carisoprodol concentration and its conversion to meprobamate, and quantify the intra-subject and inter-subject variability in carisoprodol metabolism. Liquid chromatography-tandem mass spectrometry was used to quantitate carisoprodol and meprobamate concentrations in urine specimens. The log creatinine-corrected carisoprodol versus log creatinine-corrected meprobamate showed a marginal positive relationship (R(2) = 0.395), with a 29.1-fold variance between subjects at the mean carisoprodol concentration. The geometric mean carisoprodol and meprobamate urine concentrations were 0.519 ± 3.38 mg and 28.2 ± 2.34 mg analyte per gram creatinine, respectively. The log metabolic ratio (MR) versus log creatinine-corrected carisoprodol displayed a marginal positive correlation. A subpopulation of outliers with higher carisoprodol and lower meprobamate levels were considered poor metabolizers and represented 0.483% (n = 21) of the study population. Using a curve-fit mathematical model, we estimated 0.318% (n = 10) to be ultra-rapid metabolizers. The inter-subject population geometric standard deviation (SD) of the MR was 3.64. The intra-subject geometric median and mean SD of the MR were 1.60 (interquartile range: 1.28, 2.07) and 1.72 ± 1.60, respectively. Inter-subject variability was 2.27 times greater than the median intra-subject variability. With a better understanding of urine carisoprodol and meprobamate concentrations and variability, urine drug testing provides a useful monitoring reference for clinicians.