The Pharmaceutical Journal
Vol 280 No 7498 p482-483
19 April 2008

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Propofol has withstood the test of 20 years at the forefront of anaesthesia

In the seventh article in a series on landmark drugs, Jenny Bryan looks at propofol, an intravenous anaesthetic that remains in mainstream use

Landmark drugs series

SUMMARY

When the intravenous anaesthetic propofol (Diprivan) was launched in the UK in 1986, it could not have arrived at a better time. For two years anaesthetists had been relying mainly on the barbiturates thiopentone and methohexitone to put patients to sleep, following the withdrawal of the widely used steroid agent Althesin in 1984 owing to severe allergic reactions to its solvent. The barbiturates had the drawback that people were drowsy for long periods after they woke up from surgery, so the short-acting propofol was a welcome arrival.

“The loss of Althesin was very significant because it was very useful for minor procedures, and there was less accumulation than with the barbiturates, so it could be given in multiple injections. When propofol came along, it filled the hiatus which had been left by Althesin’s withdrawal,” recalls David Greaves, consultant anaesthetist at the Royal Victoria Infirmary, Newcastle-upon-Tyne.

Propofol (2,6-diisopropylphenol) was discovered in the early 1970s at the research laboratories of ICI, and early dose ranging studies suggested that it compared well with Althesin. While its lipophilicity ensured that propofol could cross the blood brain barrier, its lack of water solubility resulted in formulation difficulties.

Initially formulated in the same cremophor EL solvent that proved the undoing of Althesin, propofol was subsequently reformulated in a soya bean emulsion that produced significantly smoother induction of anaesthesia than thiopentone and methohexitone, and superior post-anaesthetic recovery.

Today’s formulation of propofol has an additional lipid component, though a variety of experimental formulations have been tested, including a water-soluble prodrug formulation, and a sublingual product. However, none of these has overcome the fundamental problem that propofol injections hurt.

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