title: 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.
authors.affiliation: University of California, San Diego (UCSD), Skaggs School of Pharmacy & Pharmaceutical Sciences, La Jolla, CA, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Tse
authors.forename: Rabia S
authors.initials: RS
authors.lastname: Atayee
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
authors.forename: Amadeo J
authors.initials: AJ
authors.lastname: Pesce
mesh_terms: D002328:Carisoprodol / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D059350:Chronic Pain / Q000188:drug therapy* / Q000378:metabolism; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008620:Meprobamate / Q000652:urine*; D008954:Models, Biological; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics* / Q000652:urine; D012016:Reference Values; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D016482:Urinalysis
chemical_list: D009125:Muscle Relaxants, Central; D002328:Carisoprodol; D008620:Meprobamate