Factors affecting carisoprodol metabolism in pain patients using urinary excretion data.
Carisoprodol is a skeletal muscle relaxant prescribed to treat pain. Carisoprodol is metabolized to meprobamate, an active metabolite with anxiolytic effects, by the genetically polymorphic CYP2C19 enzyme. Concomitant use of CYP2C19 substrates or inhibitors may alter carisoprodol metabolism, with therapeutic and/or toxic implications for effectively treating patients with pain. This was a retrospective analysis of urinary excretion data collected from patients with pain from March 2008 to May 2011. Carisoprodol and meprobamate urine concentrations were measured by liquid chromatography-tandem mass spectrometry, and the metabolic ratio (MR) of meprobamate to carisoprodol concentrations was determined in 14,965 subjects. The MR geometric mean and 95% confidence interval (95% CI) of the young group (105, 95% CI = 99.1-113) were ∼47.4% higher than the middle-aged group (71.9, 95% CI = 70-73.8) and nearly two times higher than the elderly group (54.4, 95% CI = 51.3-57.6). Females had a 20.7% higher MR compared with males. No significant change in the MR was observed with overall CYP2C19 inhibitor or substrate use. However, evaluation of individual inhibitors showed co-administration with esomeprazole or fluoxetine was associated with a 31.8 and 24.6% reduction in MR, respectively, compared with controls (P < 0.05). Omeprazole did not significantly affect the MR. Patient-specific factors such as age, sex and co-medications may be important considerations for effective carisoprodol therapy.
1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego (UC San Diego), 9500 Gilman Drive, MC 0719, La Jolla, CA 92093-0719, USA.
Stephanie A
SA
Tse
Rabia S
RS
Atayee
Joseph D
JD
Ma
Brookie M
BM
Best
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002328:Carisoprodol / Q000493:pharmacokinetics* / Q000652:urine*; D002853:Chromatography, Liquid; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D064098:Esomeprazole / Q000008:administration & dosage; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008620:Meprobamate / Q000493:pharmacokinetics / Q000652:urine; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics* / Q000652:urine*; D010146:Pain / Q000188:drug therapy*; D012189:Retrospective Studies; D013048:Specimen Handling; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D009125:Muscle Relaxants, Central; D005473:Fluoxetine; D002328:Carisoprodol; D008620:Meprobamate; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole