Perhexiline was first marketed in France during the 1970s as a treatment for angina. But concern over its side-effects, especially fatal cases of liver damage, led to withdrawal in the UK, while in some countries it was never licensed at all. Indeed, some argue that "its use should be completely avoided."(1)
The dangers were not predicted by animal tests 2 and administration of high doses to several species for up to 2 years produced no effect on the liver.(3) According to Richardson Merrell, the company marketing perhexiline, "...there has been an inordinate amount of animal work done..At this point we simply have been unable to induce hepatic (liver) disease in any species." (4)
Perhexiline's harmful effects arise in individuals whose body chemistry has been altered by genetic factors, making them more sensitive to the drug. Reliance on animal tests can therefore be seriously misleading since they provide no basis for such subtle predictions.
1) D.G.McDevitt & A.M.MacConnachie in Meyler's Side Effects of Drugs, IIth edition,Ed.M.N.G.Dukes (Elsevier,1988).
2) C.T.Eason et al, Regulatory Toxicology & Pharmacology, 1990, vol.11, 288-307.
3) J.W.Newberne, Postgraduate Medical Journal, 1973, vol.49, April Suppl., 125-129.
4) ibid, p.l30.
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