Monograph
M03BB03 - Chlorzoxazone |
Propably not porphyrinogenic |
PNP |
Rationale
Chlorzoxazone is a substrate of CYP2E1. It is most probably not an inhibitor or inducer of any CYP enzymes in vivo.
Therapeutic characteristics
Chlorzoxazone is a muscle relaxant.
Metabolism and pharmacokinetics
Chlorzoxazone is metabolised primarily by CYP2E1 to 6-hydroxychlorzoxozone (Pelkonen 2008 and SPC).
In vitro studies indicates that chlorzoxazone is also metabolised by CYP1A1 (Masimirembwa 1999), CYP1A2 (Masimirembwa 1999 and Ono 1995) and CYP3A4 (Lucas 1999). It is also listed as a weak inhibitor of CYP3A4 in vitro (Zhou 2007).
However, co-administration of grapefruit juice (inhibitor of CYP3A4) with chlorzoxazone did not significantly modify the chlorzoxazone metabolic ratio (Lucas 1999). This indicates that chlorzoxazone is not a substrate of CYP3A4 in vivo.
No drug-drug interactions with chlorzoxazone as a perpetrator regarding CYP enzymes are observed (Interaktionsdatabasen and Legemiddelverket), which indicates that chlorzoxazone is not an inhibitor or inducer of CYP enzymes in vivo.
Personal communication
C Andersson: 2 observations of tolerance.
Published experience
The Summary of Product Characteristics warns against the use of chlorzoxazone for patients with porphyria because it can exacerbate acute attacks.
IPNet drug reports
Uneventful use reported in 5 patients with acute porphyria.
Attack report: See the monograph of M03BB53: chlorzoxazaone, combinations excl. psykoleptics. Apart from chlorzoxazone the combination may consist of dextropropoxyphen and acetylsalicylic acid (other combinations are possible). Dextropropoxyphen is classified as Porphyrinogenic (P) and is most probably the causative drug for the attack.
References
| # | Citation details | PMID |
|---|---|---|
| * | Scientific articles | |
| 1. | Chlorzoxazone, a selective probe for phenotyping CYP2E1 in humans.
Lucas D, Ferrara R, et al. Pharmacogenetics. 1999 Jun;9(3):377-88. |
|
| 2. | Heterologous expression and kinetic characterization of human cytochromes P-450: validation of a pharmaceutical tool for drug metabolism research.
Masimirembwa CM, Otter C, et al. Drug Metab Dispos. 1999 Oct;27(10):1117-22. |
10497136 |
| 3. | Chlorzoxazone is metabolized by human CYP1A2 as well as by human CYP2E1.
Ono S, Hatanaka T, et al. Pharmacogenetics. 1995 Jun;5(3):143-50. |
7550365 |
| 4. | Inhibition and induction of human cytochrome P450 enzymes: current status.
Pelkonen O, Turpeinen M, et al. Arch Toxicol. 2008 Oct;82(10):667-715. |
18618097 |
| 5. | Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring.
Zhou SF, Xue CC, et al. Ther Drug Monit. 2007 Dec;29(6):687-710. |
18043468 |
| * | Drug interaction databases | |
| 6. | Interaktionsdatabasen. Klorzoxazon
|
|
| 7. | Legemiddelverket. Interaksjonssøk. Klorzoxazon
|
|
| * | Summary of Product Characteristics | |
| 8. | Swedish National Formulary. FASS. Summary of Product Characteristics (SPC). Klorzoxazon. www.fass.se
|
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