The porphyrinogenic effect of simvastatin in experimental systems.
Attacks of acute hepatic porphyria have been previously reported to be frequently associated with transient hypercholesterolemia. This investigation was undertaken in order to establish whether the hypocholesterolemic effect of simvastatin (MK-733) is associated with inhibition of porphyrin metabolism. In two experimental models of acute hepatic porphyria--monolayers of chick embryo liver cells induced by DDC, and diethoxycarbonyl dihydrocollidine (DDC) injected rats--simvastatin was shown to increase porphyrin formation. A similar increasing effect was observed in a system which mimics the latent phase of porphyria, non-induced monolayers of chick embryo liver cells. We conclude that simvastatin is a porphyrogenic drug and should therefore be used with extreme caution in patients with hypercholesterolemia who also have latent porphyria. Its administration should be discontinued, at least temporarily, in patients with hypercholesterolemia during acute attacks of hepatic porphyria.
Schoenfeld
N
N
Laboratory of Biochemical Pharmacology, Beilinson Medical Center, Petah Tiqva, Israel.
Mamet
R
R
Lurie
Y
Y
Green
P
P
Bomstein
Y
Y
Atsmon
A
A
D000622:Aminolevulinic Acid / Q000652:urine; D000818:Animals; D000924:Anticholesteremic Agents / Q000633:toxicity*; D002642:Chick Embryo; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D011164:Porphyrias / Q000139:chemically induced*; D011166:Porphyrins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D019821:Simvastatin
D000924:Anticholesteremic Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid; D008148:Lovastatin; D019821:Simvastatin