N07XX04 - Sodium Oxybate |
Propably not porphyrinogenic |
PNP |
Rationale
Sodium oxybate is not listed as an inducer or inhibitor of cytochrome P450 enzymes and no pharmacokinetic interactions has been observed. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake. No other physiological effects of relevance for Cyp-induction.
Chemical description
Sodium oxybate is the sodium salt of gamma hydroxybutyric acid, commonly abbreviated GHB. It is an endogenous carboxylic acid derivative.
Therapeutic characteristics
Sodium oxybate is used in the management of narcolepsy and in general anaesthesia. It is administered orally or intravenously. Common adverse reactions of sodium oxybate that can be confused with an acute porphyric attack are nausea, vomiting, abdominal pain, hypertension, confusion and anxiety. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake. Weight reduction is common when using sodium oxybate. Infections such as nasopharyngitis and sinusitis are listed as common side effects, and infections are known triggers for porphyric attacks.
Metabolism and pharmakokinetics
Sodium oxybate is metabolised in the liver via gamma hyrooxybutyrate dehydrogenase to succinic semialdehyde, and then converted to succinic acid by succinic semialdehyde dehydrogenase. Succinic acid enters the Krebs cycle and is metabolised to carbon dioxide and water and is eliminated via the lungs. According to the SPC (Xyrem) in vitro data indicate that sodium oxybate does not inhibit the cytochrome P-450 (CYP) isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 and no pharmacokinetic interactions are observed between sodium oxybate and tramadol, duloxetin, lorazepam, zolpidem, protriptyline and modafinil. Half-life elimination is 30 to 60 minutes.
Preclinical data
In a study on chick embryo livers in ovo, sodium oxybate was not found to induce 6-aminolevulinate synthetase or to cause accumulation of porphyrins and cytocrome P450, and was therefore suggested to be a safe drug in acute porphyria. (Verneuil 1983)
of porphyrins and cytochrome P-450. and is suggestet by the authors to be non-porphyrogenic.
References
- Scientific articles
- de Verneuil H, Deybach JC, Study of anaesthetic agents for their ability to elicit porphyrin biosynthesis in chick embryo liver. Biochem Pharmacol 1983 Mar 15;32(6):1011-8 #2828
- Drug reference publications
- DrugBank. Gamma Hydroxybutyric Acid. #2829
- Sweetman SC, editor. Martindale: The complete drug reference. Sodium oxybate. Pharmaceutical Press 2009. #2830
- Government bodies
- European Public Assessment Report, Xyrem. (Scientific discussion).European Medicines Agency (EMEA). Accessible from: emea.europa.eu #2827
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Xyrem. #2831
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