Mainly for non-fasting occasional use and use in pre-pubertal children. Non-Cyp3A4/2C9 metabolism. No reports of interactions with Cyp-metabolism of other drugs. Mainly for pediatric use. Avoid other use than occasional. Avoid in fasting and in patients with chronic alcohol consumption.

Trichlorethane diol M=302. Very soluble in water.

Used mainly in pediatrics as short term management of insomnia, for sedation and as a sedative for premedication. Extempore formula. Peroral solution 70 mg/mL. Hypnotic dose: 0.5-2 g as single dose at night. Sedative dose: 250 mg three timers daily to a maximum daily dose of 2 g. Hypnotic and sedative with CNS-effects similar to barbiturates. Physiological effects and bye-effects of possible relevance to acute porphyria: PXR-ACTIVATION VIA OXIDATIVE STRESS. Cyp2E1 is one of the components of the microsomal ethanol oxidizing system induced in chronic alcohol consumption. In rodents and humans Cyp 2E1-metabolism of chloral hydrate and its metabolites gives rise to free radicals, diminishes reduced GSH and thereby impairs defence systems against oxidative stress, promoting the formation of lipid oxidation products (PMID15554233). Under hypoglycemic conditions oxidative stress activates stress-responsive Jun-N-terminal kinases which take part in the nuclear translocation of the PXR-coactivator FOXO1 (Thunell. Genomic approach to acute porphyria. Physiol Res 2006; 55:S43-S66). HEPATOCELLULAR CANCER. Trichloroethylene (TCE) exposure has been associated with increased risk of liver end kidney cancer in both laboratory animal and human epidemiologic studies. Studies on the TCE and chloral hydrate metabolites TCA and DCA suggest that they are involved in TCE-induced liver tumorigenesis, and that many DCA-effects are consistent with conditions that increase the risk for liver cancer in humans (PMID 16966105). However, a recent cohort study did not support a relation between the use of chloral hydrate and liver cancer (Hasselkorn et al. Drug safety 2006; 29:67-77). Low level exposure to TCE or chloral hydrate is not likely to induce liver cancer in humans, even if higher exposure could affect sensitive populations (PMID 10807555), including carriers of acute porphyria. Confounding side effects: Gastric irritation, initial vomiting, abdominal distension, paradoxical excitement, hallucinosis, confusion including paranoia.

Probably over uM hepatic exposure.

Chloral hydrate is the initial biotransformation product of trichloroethylene and is also a bye-product of water chlorination. After administration in humans it is rapidly metabolised in erythrocytes, liver and other tissues to dicloroacetate (DCA), tricloracetate (TCA) and triclorethanol, which is the active metabolite passing into CNS. Dichloroacetate is primarily transformed to glyoxylate by glutathione/maleyloacetate isomerase, which also catalyzes the penultimate step in phenylalanine and tyrosine catabolic pathways (PMID 20920954). Metabolism takes place by Cyp2E1 oxidation (PMID 11803702) and conjugation of oxidation products with glutathione. Involvement of Cyp 3A4 is minimal (PMID 9070354). The metabolites are excreted in urine as tricloroacetic acid and as tricloroethanol and its glucuronide. The very high solubility in water indicates low PXR-affinity. No Cyp-dependent drug interactions listed.

Uneventful use reported in 1 patient with acute porphyria.