Pharmacogenetics. 1996 Oct;6(5):387-94.
Formation of meprobamate from carisoprodol is catalysed by CYP2C19.

Dalen P, Alvan G, Wakelkamp M, Olsen H.

Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.

Carisoprodol is a muscle relaxant analgesic, which has an active metabolite i.e. meprobamate. We conducted an open three-panel single-dose administration study with 15 healthy volunteers: five poor metabolizers of mephenytoin, five poor metabolizers of debrisoquine and five extensive metabolizers of both substrates. The aim was to investigate if the elimination of carisoprodol and meprobamate is dependent on the two metabolic polymorphisms of mephenytoin and debrisoquine. The subjects were given single oral doses of 700 mg carisoprodol and 400 mg meprobamate on separate occasions. The disposition of carisoprodol was clearly correlated to the mephenytoin hydroxylation phenotype. The mean serum clearance of carisoprodol was four times lower in poor metabolizers of mephenytoin than in extensive metabolizers, which confirms the hypothesis from our previous study that N-dealkylation of carisoprodol cosegregates with the mephenytoin hydroxylation polymorphism. However, mean serum clearance of meprobamate did not differ between the two groups. Also, polymorphic debrisoquine hydroxylation did not influence the elimination of carisoprodol or meprobamate. Poor metabolizers of mephenytoin thus have a lower capacity to metabolize carisoprodol and may therefore have an increased risk of developing concentration dependent side-effects such as drowsiness and hypotension, if treated with ordinary doses of carisoprodol.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8946470&dopt=Abstract soma carisoprodol




South Med J. 1998 Aug;91(8):726-30.
A review of carisoprodol deaths in Jefferson County, Alabama.

Davis GG, Alexander CB.

Department of Pathology, University of Alabama at Birmingham, USA.

BACKGROUND: Carisoprodol is a skeletal muscle relaxant with the potential for abuse. A carisoprodol overdose is rarely considered fatal. Nevertheless, we encountered carisoprodol in several cases, prompting review of our experience. METHODS: We did a retrospective study of cases examined at the Jefferson County Coroner/Medical Examiner Office from January 1, 1986, to October 31, 1997, reviewing investigative reports and autopsy findings. RESULTS: Carisoprodol was present in 24 cases. Seventeen decedents died of acute drug intoxication. Carisoprodol was never the sole drug detected at autopsy, nor was it ever the sole cause of death. Propoxyphene was a co-intoxicant in 8 of the 24 cases. CONCLUSIONS: Carisoprodol causes respiratory depression. Since the mechanism of death was respiratory depression in 82% of the decedents who died of acute intoxication, we consider that carisoprodol was probably responsible, in part, for those deaths. The simultaneous use of propoxyphene and carisoprodol seems to be especially dangerous.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9715216&dopt=Abstract soma carisoprodol




J Am Osteopath Assoc. 2003 Feb;103(2):75-80.
Somatic dysfunction during carisoprodol cessation: evidence for a carisoprodol withdrawal syndrome.

Reeves RR, Parker JD.

G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi, Jackson 39216, USA. roy.reeveed.va.gov

Carisoprodol is a commonly used skeletal muscle relaxant with potential for abuse because of its active metabolite, meprobamate, and several reports have suggested that patients abruptly stopping intake of carisoprodol may have a withdrawal syndrome. The authors studied changes in the occurrence of somatic dysfunctions in five patients during an 8-day period following discontinuation from large doses of carisoprodol. Results showed that the number of somatic dysfunctions changed significantly during the withdrawal period. Each patient had an increase in the number of somatic dysfunctions during the first 3 days after cessation of carisoprodol with return to at or near baseline by the eighth day. This was reflected statistically in a significant-within-subjects effect for time. Results of supplemental analyses revealed a significant component of the effect and a trend for the quadratic component to be significant. Increases in the number of somatic dysfunctions during carisoprodol discontinuation support the existence of a carisoprodol withdrawal syndrome.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12622352&dopt=Abstract soma carisoprodol