化合物信息

Drug Groups

approved; investigational

Description

Propofol is an intravenous anaesthetic agent used for induction and maintenance of general anaesthesia. IV administration of propfol is used to induce unconsciousness after which anaesthesia may be maintained using a combination of medications. Recovery from propofol-induced anaesthesia is generally rapid and associated with less frequent side effects (e.g. drowsiness, nausea, vomiting) than with thiopental, methohexital, and etomidate. Propofol may be used prior to diagnostic procedures requiring anaesthesia, in the management of refractory status epilepticus, and for induction and/or maintenance of anaesthesia prior to and during surgeries.

Indication

Used for induction and/or maintenance of anaesthesia and for management of refractory status epilepticus.

Pharmacology

Propofol is a sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Intravenous injection of a therapeutic dose of propofol produces hypnosis rapidly with minimal excitation, usually within 40 seconds from the start of an injection (the time for one arm-brain circulation).

Toxicity

Overdosage may increase pharmacologic and adverse effects or cause death.

IV LD₅₀=53 mg/kg (mice), 42 mg/kg (rats). Oral LD₅₀ (as a solution in soybean oil)=1230 mg/kg (mice), 600 mg/kg (rats)

Affected Organisms

Biotransformation

Hepatically metabolized mainly by glucuronidation at the C1-hydroxyl. Hydroxylation of the benzene ring to 4-hydroxypropofol may also occur via CYP2B6 and 2C9 with subsequent conjugation to sulfuric and/or glucuronic acid. Hydroxypropofol has approximately 1/3 of hypnotic activity of propofol.

Absorption

Rapid - time to onset of unconsciousness is 15-30 seconds, due to rapid distribution from plasma to the CNS. Distribution is so rapid that peak plasma concentrations cannot be readily measured. Duration of action is 5-10 minutes.

Half Life

Initial distribution phase t_1/2α=1.8-9.5 minutes. Second redistirubtion phase t_1/2β=21-70 minutes. Terminal elimination phase t_1/2γ=1.5-31 hours.

Protein Binding

95 to 99%, primarily to serum albumin and hemoglobin

Elimination

It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney.

Distribution

* 60 L/kg [healthy adults]

Clearance

* 23 - 50 mL/kg/min
* 1.6 - 3.4 L/min [70 Kg adults]

References

External Links