CLINICAL PHARMACOLOGY
Carisoprodol is a centrally acting skeletal muscle relaxant that does not directly relax tense skeletal muscles in man. The mode of action of carisoprodol in relieving acute muscle spasm of local origin has not been clearly identified, but may be related to its sedative properties. In animals, carisoprodol has been shown to produce muscle relaxation by blocking interneuronal activity and depressing transmission of polysynaptic neurons in the spinal cord and in the descending reticular formation of the brain. The onset of action is rapid and lasts four to six hours.
Carisoprodol is metabolized in the liver and is excreted by the kidneys. One of the products of metabolism, meprobamate, is active as an anxiolytic. The degree to which it contributes to the efficacy of carisoprodol is unknown. Carisoprodol is dialyzable by peritoneal and hemodialysis.
Absorption, Distribution, Metabolism, Excretion
Following a single oral dose of carisoprodol, the time to maximum concentration (Tmax) was 1.98 ¡À 1.16 hours and the terminal elimination half-life was 2.44 ¡À 0.93 hours. By normalizing to a single 350 mg carisoprodol tablet, the mean peak plasma concentration (Cmax) was 2.29 ¡À- 0.68 ug/mL, the area under the plasma level time curve (AUC 0-¥ ) was 10.33 ¡À 3.87 ug/mL* hour, and the oral clearance (Cl/F) was 39.52 ¡À 16.83 L/hour. The mean Cmax of metabolite, meprobamate, was 2.08 ¡À 0.48 ug/mL, a subtherapeutic concentration when compared to a plasma concentration of a single oral meprobamate 400 mg tablet which would yield a meprobamate concentration of approximately 8.0 ug/mL.
Pharmacokinetics
Absorption
The pharmacokinetics of carisoprodol was determined in a small in vivo biostudy of 5 men and 5 women. When the dose was normalized to 350 mg, the mean peak plasma concentration (Cmax) achieved was 2.29 ¡À 0.68 ug/mL. Women tended to reach peak plasma concentrations earlier than men (1.45 vs. 2.5 hours) and had a faster apparent oral clearance (0.772 vs. 0.38 L/hour/kg). The clinical significance of these findings is unknown and they may in part be due to the small number of subjects present in the trial.
Metabolism
Carisoprodol is metabolized in the liver via cytochrome P450 enzyme, CYP2C19. This enzyme exhibits genetic polymorphism. For example, 15-20% of Asian populations may be expected to be poor metabolizers. For Caucasians and Blacks, the prevalence of poor metabolizers is 3-5%. Following a single 350 mg dose of carisoprodol, the corresponding normalized peak concentration of meprobamate, which is a metabolite of carisoprodol, was 2.08 ¡À 0.48 ug/mL. These levels are approximately ¼ of those seen following a single 400 mg dose of meprobamate.
Elimination
Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of 2.44 ¡À 0.93 hours. It is dialyzable by peritoneal and hemodialysis.
Special Populations
The pharmacokinetic profile of carisoprodol in patients with renal impairment or hepatic impairment has not been evaluated. Because carisoprodol is metabolized by the liver and excreted by the kidneys, possible increased exposure of carisoprodol is expected if hepatic and/or renal function is impaired. The drug should be used with caution in patients with impaired hepatic or renal function.
The pharmacokinetic profile of carisoprodol in elderly patients has not been evaluated
