ADMET-Absorption, Distribution, Metabolism, Excretion, and Toxicity

Absorption_value98.0
Absorption (description)Readily absorbed after oral administration with peak plasma levels occurring after 2 to 4 h
Caco_2-4.7
Bioavailability25.0

MetabollsmHepatic, mostly CYP2D6-mediated. it undergoes first-pass metabolism in the gut wall and is extensively metabolised in the liver and excreted in the bile and urine. Metabolism is catalysed by the P450 isoenzyme CYP2D6 and includes sulfoxidation, N-demethylation, hydroxylation, N-oxidation; glucuronic acid conjugation and possibly ring fission also occur. There is some evidence that chlorpromazine may stimulate its own metabolism. A large number of metabolites have been isolated and some of the metabolites are active, particularly 7-hydroxychlorpromazine, although less so than the parent drug; several metabolites may be detected in plasma at concentrations similar to those of chlorpromazine during chronic treatment.
Half life7~120 h; mean values are usually in the range 15 to 30 h.

ExcretionAbout 20 to 70% of an oral dose is excreted in the urine as metabolites, mostly conjugated, with 5% of the dose as the sulfoxide, and less than 1% as unchanged drug; about 5% of a dose is eliminated in the faeces as metabolites. Chlorpromazine metabolites have been detected in urine up to 18 months after discontinuation of long-term treatment. The monodesmethyl, 7-hydroxy, and sulfoxide metabolites are taken up by erythrocytes along with traces of the parent drug and its N-oxide. Chlorpromazine is widely distributed in the body. It crosses the blood–brain barrier with levels in the brain higher than those in plasma. Chlorpromazine and its metabolites cross the placenta and are found in breast milk.
Urinary Excretion<1
Clerance8.6 ml/min/kg.

ToxicitySevere toxic symptoms have occurred with doses of less than 0.1 g. Overdosage with chlorpromazine is a fairly common occurrence, but fatalities are relatively rare. Blood concentrations in the region of 0.5 to 2 mg/L are associated with toxic effects and concentrations of 2 mg/L or greater may be lethal. In a review of 8 fatal cases, blood concentrations of 3 to 35 mg/L (mean 17), and liver concentrations of 54 to 2110 μg/g (mean 366) were reported [R. Bonnichsen et al.,Z. Rechtsmed.,1970, 67, 158–169].
LD50 (rat)N/A
LD50 (mouse)N/A