Testicular Function in Type II Hyperlipoproteinemic Patients Treated with Lovastatin (Mevinolin) or Neomycin

Farnsworth, Wendy; Hoeg, Jeffrey M.; Maher, Martha B.; Brittain, Emily; Sherins, Richard J.; Brewer, H. Bryan

doi:10.1210/jcem-65-3-546

Cited by 53 publications

(27 citation statements)

References 22 publications

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“…Results from clinical trials with lovastatin [23, 24| have not shown any adverse effects on hematologic parameters. Sperm counts were not significantly altered by lovastatin therapy [28]. These observa tions provide indirect evidence that tissue lev els of isopentenyl adenine are not adversely affected by therapeutic doses of HMG CoA reductase inhibitors.…”

Section: Isopentenyl Adeninementioning

confidence: 63%

Long-Term Clinical Tolerance of Lovastatin and Simvastatin

Bilheimer

1990

Cardiology

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3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors are gaining widespread use in the treatment of hypercholesterolemia. Clinical experience with lovastatin, which is approaching 4 years in many patients, indicates that it is well tolerated. Short-term adverse effects have usually been self-limited and have included abdominal pain, cramps, bloating, and flatus in 4-6% of cases. Raised hepatic transaminases and myopathy have occurred in 1.3 and 0.1% of cases, respectively; both, however, are reversible upon discontinuation of drug. To date, there is no evidence that lovastatin adversely affects the human lens. Overall, the drug has been well tolerated by the vast majority of patients over the long term. Early clinical experience with simvastatin shows a pattern and frequency of side effects similar to that reported with lovastatin.

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Section: Isopentenyl Adeninementioning

confidence: 63%

Long-Term Clinical Tolerance of Lovastatin and Simvastatin

Bilheimer

1990

Cardiology

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“…Some studies have shown that the non-absorptive polybasic antibiotic neomycin in vitro induced the precipitation of mixed micelle solution, and in vivo reduced the plasma lipids in type II hyperlipoproteinemia. 21,22 As protamine is a polybasic peptide, we suggest that its lowering lipid effect might be because of the same mechanism as neomycin.…”

Section: Discussionmentioning

confidence: 92%

Effect of protamine in obesity induced by high-fat diets in rats

et al. 2009

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Objective: Protamine has been shown to have an inhibitory effect on protein lipase in vitro; the objective of this study was to evaluate the antiobesity activity effect of protamine in obese induced rats, and to evaluate the effect of protamine on postprandial hypertriacylglyceridemia in rats by intragastric administration of a lipid emulsion containing corn oil. Design: Two experiments were carried out: (1) In a parallel study in rats, we administered a lipid emulsion containing corn oil plus 0, 200 or 500 mg kg -1 of protamine intragastrically. (2) In a randomized parallel prospective rats experiment, rats were fed with a high-fat diet and 0, 200 or 500 mg of protamine per kg of animal weight during 5 weeks. Subjects: Male Sprague-Dawley rats. Measurements: In experiment 1, plasma triacylglycerol levels after oral administration of lipid emulsion were determined. In experiment 2, weight gain, concentrations of plasma triacylglycerol, plasma total cholesterol and albumin were determined, and the subcutaneous and visceral adipose tissues were weighed. Results: Plasma triacylglycerol concentration in rats administered with 200 or 500 mg kg -1 of protamine was significantly lower than that in rats in the control group (200 mg kg -1 of protamine, Po0.05 at 1, 2, 3 and 4 h; 500 mg kg -1 of protamine Po0.05 at 2, 3 and 4 h). In rats fed with a high-fat diet, and 200 and 500 mg kg -1 of protamine, there was a decreased body weight gain by 52 and 66 g, respectively, reduced visceral fat by 5 and 8 g, respectively and subcutaneous tissue weights by 12 and 15 g, respectively. Plasma triacylglycerol was 17 and 45 mg per 100 ml lower in rats fed with high-fat diet plus 200 and 500 mg kg -1 of protamine, respectively. And cholesterol concentrations were 18 and 22 mg per 100 ml lower in both protamine groups, respectively. Conclusion: Our study demonstrates that protamine reduce weight gain and body fat accumulation through the inhibition of dietary fat absorption.

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“…Preclinical studies have shown that serum testosterone and luteinizing hormone levels were not affected by administration of lovastatin, simvastatin or cerivastatin to dogs. In clinical studies, with the exception of a slight decrease in sperm motility, indicators of testicular function (including sperm counts and morphology and serum androgen levels) were not altered in men treated with lovastatin or simvastatin (Farnsworth et al, 1987;Purvis et al, 1992).…”

Section: Testicular Effectsmentioning

confidence: 86%

The Toxicology of HMG—CoA Reductase Inhibitors: Prediction of Human Risk

Macdonald¹,

Halleck

2004

Toxicol Pathol

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The discovery that 3-hydroxy-3-methyglutaryl coenzyme A reductase was a rate-determining step in the biosynthesis of cholesterol led to the discovery of inhibitors of this enzyme. To support the development of these agents (statins) as potential hypocholesterolemic drugs, a variety of preclinical studies were conducted in several animal species. Not unexpectedly due to the central role played by mevalonic acid and its products including cholesterol in development and maintenance of cellular homeostasis, administration of high dosage levels of these agents led to the expression of a broad variety of adverse effects in many different tissues. Using the tools of toxicologic pathology and classical risk assessment, these varied toxicities were evaluated by many groups relative to the conditions of use in human therapy and a perspective was developed on potential human risk. These approaches of mechanism-based risk assessment predicted that most of the adverse effects observed in animals would not be seen under conditions of human use and supported the successful introduction of one of the most important classes of human medicines.

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Testicular Function in Type II Hyperlipoproteinemic Patients Treated with Lovastatin (Mevinolin) or Neomycin

Cited by 53 publications

References 22 publications

Long-Term Clinical Tolerance of Lovastatin and Simvastatin

Long-Term Clinical Tolerance of Lovastatin and Simvastatin

Effect of protamine in obesity induced by high-fat diets in rats

The Toxicology of HMG—CoA Reductase Inhibitors: Prediction of Human Risk

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