Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

Etoricoxib

Etoricoxib is a highly selective COX-2 inhibitor that has a UK license but is awaiting

FDA approval. It is a methylsulphone.

Ithas been shown to be efficacious in providing effective pain control when com-

pared to COX-1 inhibitors. It has a COX-1:COX-2 inhibitory ratio of 1:344.

Kinetics

Etoricoxib is absorbed efficiently producing an oral bioavailability of > 95%. It has a

volume of distribution of 1.5 l.kg–1and is 90% plasma protein bound. Its elimination

half-life is 22 hours. It is metabolized in the liver through cytochrome P450 oxidation,

CYP3A4 being the predominant isoenzyme. However, other isoenzymes are involved

and may become more involved with specific CYP3A4 inhibition. It is a weak inhibitor

of CYP-2D6, -3A, and -2C9. Its elimination half-life increases in hepatic failure, but

in isolated renal failure no change is seen.

Itsside effects (or lack of them) are predictable. Its rate of gastric irritation is sim-

ilar to placebo and significantly lower than COX-1 inhibitors, although this effect

decreases beyond 9–12 months therapy. There is currently insufficient data to con-

firm that etoricoxib will be free from the cardiovascular effects that caused rofecoxib

to be withdrawn from the market.

Lumaricoxib

Lumaricoxib is a phenylacetic acid derivative and as such is structurally different

from the other COX-2 inhibitors, bearing a closer resemblance to diclofenac. It has

aCOX-1:COX-2 inhibitory ratio of 1:700. Due to its structure it has a lower volume of

distribution compared with the other COX-2 inhibitors.

Following reports of serious hepatoxicity including cases resulting in death or liver

transplantation, lumaricoxib is now contraindicated in patients with any current

liver disease or a history of drug induced elevation of transaminases. In addition

liver function tests are required during treatment.

Kinetics

Ithas the shortest elimination half-life of 5 hours.