Carisoprodol

Absorption

Absorption
The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a crossover study of 24 healthy subjects (12 male and 12 female) who received single doses of 250 mg and 350 mg carisoprodol (see Table 2). The exposure of carisoprodol and meprobamate was dose proportional between the 250 mg and 350 mg doses. The C
max of meprobamate was 2.5 ± 0.5 μg/mL (mean ± SD) after administration of a single 350 mg dose of carisoprodol, which is approximately 30% of the Cmax of meprobamate (approximately 8 μg/mL) after administration of a single 400 mg dose of meprobamate.
Table 2. Pharmacokinetic Parameters of Carisoprodol and Meprobamate
(Mean ± SD, n=24)
250 mg Carisoprodol
350 mg Carisoprodol
Carisoprodol
C
max (μg/mL)
1.2 ± 0.5
1.8 ± 1.0
AUC
inf (μg*hr/mL)
4.5 ± 3.1
7.0 ± 5.0
T
max (hr)
1.5 ± 0.8
1.7 ± 0.8
T
1/2 (hr)
1.7 ± 0.5
2.0 ± 0.5
Meprobamate
C
max (μg/mL)
1.8 ± 0.3
2.5 ± 0.5
AUC
inf (μg*hr/mL)
32 ± 6.2
46 ± 9.0
T
max (hr)
3.6 ± 1.7
4.5 ± 1.9
T
1/2 (hr)
9.7 ± 1.7
9.6 ± 1.5
Absolute bioavailability of carisoprodol has not been determined. The mean time to peak plasma concentrations (T
max) of carisoprodol was approximately 1.5 to 2 hours.
Food Effect: Co-administration of a high-fat meal with carisoprodol (350 mg tablet) had no effect on the pharmacokinetics of carisoprodol. Therefore, carisoprodol may be administered with or without food.
Elimination
Metabolism: The major pathway of carisoprodol metabolism is via the liver by cytochrome enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism (see Patients with Reduced CYP2C19 Activity below).
Excretion: Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of approximately 2 hours. The half-life of meprobamate is approximately 10 hours.
Specific Populations
Sex: Exposure of carisoprodol is higher in female than in male subjects (approximately 30 to 50% on a weight adjusted basis). Overall exposure of meprobamate is comparable between female and male subjects.
Patients with Reduced CYP2C19 Activity: Carisoprodol should be used with caution in patients with reduced CYP2C19 activity. Published studies indicate that patients who are poor CYP2C19 metabolizers have a 4-fold increase in exposure to carisoprodol, and concomitant 50% reduced exposure to meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is approximately 3 to 5% and in Asians is approximately 15 to 20%.