| Indication |
Used for induction and/or maintenance of anaesthesia and for management of refractory status epilepticus. |
| Pharmacodynamics |
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). |
| Mechanism of action |
The action of propofol involves a positive modulation of the
inhibitory function of the neurotransmitter gama-aminobutyric acid
(GABA) through GABA-A receptors. |
| 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. |
| Volume of distribution |
|
| Protein binding |
95 to 99%, primarily to serum albumin and hemoglobin |
| Metabolism |
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. |
| Route of elimination |
It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney. |
| Half life |
Initial distribution phase t1/2α=1.8-9.5 minutes. Second redistirubtion phase t1/2β=21-70 minutes. Terminal elimination phase t1/2γ=1.5-31 hours. |
| Clearance |
- 23 – 50 mL/kg/min
- 1.6 – 3.4 L/min [70 Kg adults]
|
| 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) |
