title: Bioavailability of oral carisoprodol 250 and 350 mg and metabolism to meprobamate: A single-dose crossover study.
abstract: BACKGROUND
  Carisoprodol is a skeletal muscle relaxant indicated for use in the treatment of acute, painful musculoskeletal conditions. Two randomized, controlled clinical trials have reported that carisoprodol 250 mg QID was equally effective as and better tolerated than carisoprodol 350 mg QID.
  
  
  OBJECTIVE
  The primary objective of the current study was to determine the relative bioavailability of carisoprodol and its metabolite, meprobamate, with singledose administration of 250- and 350-mg tablets. A secondary objective of the study was to determine whether lowering the carisoprodol dose would decrease plasma meprobamate concentrations.
  
  
  METHODS
  This single-dose, randomized, open-label, crossover study enrolled healthy volunteers. Each dose was administered with water in the morning; after a 7-day washout, subjects received the alternate dose. Blood samples were drawn at prespecified times over a 48-hour period. For tolerability assessment, subjects underwent a physical examination, including 12-lead ECG.
  
  
  RESULTS
  A total of 24 subjects were enrolled (12 men, 12 women; mean age, 22.8 years). The dose-adjusted AUC0-∞ values for carisoprodol were 5.29 μg/mL/h with the 250-mg tablet and 5.75 μg/mL/h with the 350-mg tablet (relative bioavailability, 92%). The mean (SD) Cmax values of carisoprodol and meprobamate after administration of the 250-mg carisoprodol tablet were 1.24 (0.49) and 1.84 (0.31) μg/mL, respectively, compared with 1.78 (0.97) and 2.46 (0.47) μg/mL with the 350-mg tablet. AUC0-∞ was dose proportional, and the apparent t1/2 values at the terminal phase were 1.74 hours with the 250-mg tablet and 1.96 hours with the 350-mg tablet. There were 3 mild adverse events considered possibly treatment related (weakness, dizziness, and drowsiness); these were reported in 2 subjects with 350-mg carisoprodol.
  
  
  CONCLUSIONS
  In this small study in healthy fasting subjects, the exposure to carisoprodol and meprobamate was dose proportional between the single 250- and 350-mg doses. Both doses were generally well tolerated.
authors.affiliation: Private practice, Leawood, Kansas.
authors.forename: Steve
authors.initials: S
authors.lastname: Simon
authors.affiliation: Meda Pharmaceuticals, Inc., Somerset, New Jersey.
authors.forename: Carrie
authors.initials: C
authors.lastname: D'Andrea
authors.affiliation: Meda Pharmaceuticals, Inc., Somerset, New Jersey.
authors.forename: William J
authors.initials: WJ
authors.lastname: Wheeler
authors.affiliation: Meda Pharmaceuticals, Inc., Somerset, New Jersey.
authors.forename: Harry
authors.initials: H
authors.lastname: Sacks
keywords: back spasm; bioavailability; carisoprodol; dose proportionality; meprobamate; muscle; oral drug delivery; pharmacokinetics