1989
DOI: 10.1016/s0002-9343(89)80596-0
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Animal safety and toxicology of simvastatin and related hydroxy-methylglutaryl-coenzyme a reductase inhibitors

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Cited by 123 publications
(80 citation statements)
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“…Mevastatin, lovastatin, mevalonate, squalene, farnesyl-pyrophosphate, geranylgeranyl-pyrophosphate, arachidonic acid, and actinomycin D were from Sigma-Aldrich. Statins in lactone form were dissolved in 0.1 M NaOH to generate the active form and the pH adjusted to 7.4 by adding 0.1 M HCl as described previously (11,12). Prenyltransferase inhibitors (farnesyltransferase inhibitor FTI-277 and geranylgeranyltransferases inhibitor GGTI-286) were from Calbiochem (La Jolla, CA).…”
Section: Methodsmentioning
confidence: 99%
“…Mevastatin, lovastatin, mevalonate, squalene, farnesyl-pyrophosphate, geranylgeranyl-pyrophosphate, arachidonic acid, and actinomycin D were from Sigma-Aldrich. Statins in lactone form were dissolved in 0.1 M NaOH to generate the active form and the pH adjusted to 7.4 by adding 0.1 M HCl as described previously (11,12). Prenyltransferase inhibitors (farnesyltransferase inhibitor FTI-277 and geranylgeranyltransferases inhibitor GGTI-286) were from Calbiochem (La Jolla, CA).…”
Section: Methodsmentioning
confidence: 99%
“…not unexpected, as the liver is the primary site of cholesterol synthesis and the primary site of drug delivery for HMGRI (1) including AT (3,17). Although transient increases in ALT and AST were described for lovastatin in dogs (up to 180 mg/kg/day) (11) and monkeys (800 mg/kg for 7 days) (12) and for simvastatin (8) (14,17). Hyperplasia and/or inflammation of gallbladder have been described in dogs given other HMGRIs (2,6).…”
Section: Introductionmentioning
confidence: 99%
“…Skeletal muscle degeneration has not been previously reported with HMGRI in dogs although it has been described in rats (8,11,16), rabbits (5), and marmosets (15) but not in cynomolgus monkeys (12). In our studies, skeletal muscle degeneration was seen in tongue of 2 dogs that had pain upon opening the mouth.…”
Section: Introductionmentioning
confidence: 99%
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“…4). Micro Increases in ALT and AST levels have been described in dogs given HMGRIs (7,8,10,15), but hepatic necrosis and degeneration were noted only with fluvastatin administration (10). Liver lesions were not reported in dogs given pravastatin for up to 104 wk (28).…”
Section: Moribund and Week 52mentioning
confidence: 99%