Effect of neomycin on exchangeable pools of cholesterol in the steady state

A B S T R A C T The mode of action of the hypocholesteremic drug neomycin (2 g/day) was studied in four patients. All showed a significant reduction in plasma cholesterol concentrations (mean 25%, range (1), and since then it has been demonstrated that a few other antibacterial drugs have similar properties. Of these kanamycin (2) and paromomycin (3) are similar in structure to neomycin, but chlortetracycline (2), chloramphenicol (4), and para-aminosalicylic acid (2) have markedly different molecular conDr. Sedaghat's present address is:

“…1 (14). Thus, in the neomycin period, the cholesterol balance represents the difference between intake and the sum of cholesterol synthesis plus cholesterol efflux from tissue stores.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of neomycin on absorption, synthesis, and/or flux of cholesterol in man.

Sedaghat¹,

Samuel²,

Crouse³

et al. 1975

“…It is not, however, known whether large neomycin doses could also increase fecal bile acid output; whether the neomycin-induced increase in fecal steroids is long-standing, as the serum cholesterol lowering is; whether the decrease in serum cholesterol is related to changes in cholesterol elimination; and whether cholesterol synthesis is compensatorily increased by the drug. Cholesterol turnover studies off and on neomycin did not reveal any significant changes in the half time of the serum cholesterol radioactivity decay curve (14), and the unchanged slope of this curve during the neomycininduced fall in serum cholesterol was interpreted to be a result of the combined action of reduced absorption, enhanced mobilization oftissue cholesterol and stimulated cholesterol synthesis (13).…”

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confidence: 97%

Effects of Neomycin Alone and in Combination with Cholestyramine on Serum Cholesterol and Fecal Steroids in Hypercholesterolemic Subjects

Miettinen¹

1979

A B S T R A C T Effects of neomycin were studied on serum cholesterol and fecal steroids in hypercholesterolemic patients during a short treatment period (4 wk) and a long treatment period (16 mo), using small (1.5 g/d) and large (up to 6 g/d) doses alone and in combination with cholestyramine. In the short-term low-dose study the decrease in serum cholesterol by 21% was associated with a proportionate increase in fecal cholesterol elimination as neutral sterols through impaired cholesterol absorption. Serum cholesterol remained low and fecal steroid excretion remained elevated in the long-term neomycin study. Increasing the dosage from 1.5 to 6 g/d at the end of the 16-mo period brought about a further slight decrease in serum cholesterol and a small further increase in fecal neutral and acidic steroids. The increases in fecal bile acids and fat but not in neutral sterols were positively correlated with the increases in the neomycin dosage. Thus, large neomycin doses can also cause bile acid malabsorption. In another series of patients, a decrease (25%) in serum cholesterol by cholestyramine was associated with a proportional increase in the fecal elimination of cholesterol (2.5-fold) as bile acids. The inclusion of neomycin in cholestyramine therapy further increased fecal steroid output (solely as neutral sterols) by only about one-fifth ofthat due to cholestyramine, but further decreased serum cholesterol almost to the same extent (-17%) as cholestyramine alone. The overall decrease was 38%, no side effects occurred, and the patients found combination therapy convenient. Neomycin decreased serum cholesterol in

“…INTRODUCTION Considerable information is now available about the turnover of plasma cholesterol in normal and in hyperlipidemic humans. When kinetic studies are conducted for periods of about 10-12 wk, the turnover of cholesterol can be described satisfactorily by a simple twopool model (1)(2)(3)(4). This model has been used to examine the relationships between some parameters of cholesterol metabolism and other clinical features such as body weight (3).…”

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confidence: 99%

“…This model has been used to examine the relationships between some parameters of cholesterol metabolism and other clinical features such as body weight (3). The kinetic approach has also been employed to assess the effects of drugs that lower serum lipids, such as cholestyramine resin (1,5,6), neomycin (2), and clofibrate (7). The effects of ileal bypass surgery on body cholesterol metabolism have been examined by the turnover technique (6,8).…”

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confidence: 99%

The Effects of Colestipol Resin and of Colestipol Plus Clofibrate on the Turnover of Plasma Cholesterol in Man

Goodman¹,

Noble²,

Dell³

1973

A B S T R A C T Studies were conducted to determine the effects of colestipol hydrochloride, a new bile acidsequestrant resin, on some of the parameters of cholesterol turnover and metabolism in man. Three normal volunteers and eight hyperlipidemic patients participated in three sets of cholesterol turnover studies carried out at intervals of approximately 1 yr. The effects of colestipol were assessed by comparing the results obtained before therapy with those obtained on repeat study after several months of resin therapy. Colestipol treatment significantly reduced the serum cholesterol concentration (mean reduction 21%), and produced a large increase in the production rate of cholesterol (mean 86%) and in the turnover rate of cholesterol in pool 1 (mean 46%). The values of the intercompartmental rate constants and of the size of the rapidly exchangeable pool were unchanged with therapy.The turnover studies were carried out for 12-13 wk, and were analyzed according to a two-pool model. Although long-term studies of cholesterol turnover conform to a three-pool, rather than a two-pool model, the present studies probably provide a valid estimate of the effects of therapy on certain parameters, namely the production rate, the size, and the turnover rate of pool 1.Repeated studies in four untreated subjects showed a striking constancy with time for the kinetic parameters for each subject. four patients, and reduced the triglyceride level in all four patients. Addition of clofibrate to the treatment program produced only small decreases in the production rate, which were not significantly different from the small decreases seen in two patients who were continued (and restudied) on colestipol alone. The findings do not support the suggestion that clofibrate can block the increased rate of cholesterol synthesis and turnover resulting from bile acid-sequestrant treatment. The effects on serum lipids, however, make the combined drug therapy potentially quite useful. INTRODUCTION Considerable information is now available about the turnover of plasma cholesterol in normal and in hyperlipidemic humans. When kinetic studies are conducted