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

StatusN/A
Administration Inhalation, Transmucosal, Intravenous, Oral, Intranasal, Rectal, Intramuscular
PharmacologyA semi-synthetic opioid drug synthesized from morphine, a derivative of the opium poppy.

Absorption_valueN/A
Absorption (description)Readily absorbed after oral administration or by injection.
Caco_2N/A
Bioavailability1.0

MetabollsmFollowing injection, it is rapidly hydrolysed to 6-monoacetylmorphine in blood and then more slowly metabolised to morphine which is the major active metabolite; normorphine is also formed to a minor extent; small quantities of codeine are occasionally seen in the urine of addicts, but this is thought to arise from the presence of acetylcodeine as an impurity in illicit heroin samples. Orally administered diamorphine undergoes extensive first-pass metabolism to morphine. All metabolites may be conjugated with glucuronic acid.
Half life3 min (diamorphine); 6~25 min (6-monoacetylmorphine); 2~3 h (morphine)

ExcretionUp to 80% of a dose is excreted in the urine in 24 h, mainly as morphine-3-glucuronide with about 5 to 7% of the dose as free morphine, 1% as 6-monoacetylmorphine, 0.1% as unchanged drug, and trace amounts of other metabolites; after inhalation, 14 to 20% of the dose appears in the urine; morphine metabolites are excreted in the bile. Diamorphine crosses the blood–brain barrier within 15 to 20 s and achieves relatively high brain levels; 68% of an intravenous dose is absorbed into the brain.
Urinary ExcretionN/A
Clerancemorphine about 15~20 ml/min/kg; new-born infants (24 to 41 weeks' gestation), 4.6 ml/min/kg

ToxicityDiamorphine is 2 to 3 times more potent than morphine. The estimated minimum lethal dose is 200 mg, but addicts may be able to tolerate up to 10 times as much; fatalities have occurred after doses of 10 mg.
LD50 (rat)N/A
LD50 (mouse)N/A