Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia.

In a single-blind, crossover, completely randomized study, the effects of oral treatment with pantethine or placebo on fatty acid composition of plasma and platelet phospholipids were investigated in 10 IIa hyperlipoproteinemic patients. A significant decrease of total cholesterol and total phospholipids was observed both in plasma and in platelets after a twenty-eight-day treatment. In plasma, pantethine induced a decrease of the ratio sphingomyelin/phosphatidylcholine. Moreover, a relative increase of n3-polyunsaturated fatty acids both in plasma and in platelet phospholipids and a decrease of arachidonic acid in plasma phospholipids were observed. These results indicate that pantethine can affect plasma and platelet lipid composition with possibly favorable influences on the determinants of cell membrane fluidity. Prisco D, Rogasi PG, Matucci M, Paniccia R, Abbate R, Gensini GF, Neri Serneri GG. Angiology 1987 Mar;38(3):241-7

PMID: 3551695 [PubMed - indexed for MEDLINE]

Changes in fatty acid composition of the single platelet phospholipids induced by pantethine treatment.

In a single-blind cross-over study the effect of oral treatment with pantethine on plasma and platelet lipid composition was evaluated in 20 patients with dyslipidaemia (7 IIa, 7 IIb and 6 Iv type). In plasma significant decreases of total cholesterol and triglycerides with increase of high density lipoprotein-cholesterol were observed. In platelets pantethine treatment significantly reduced phospholipid and cholesterol content. In addition gas-chromatographic analysis showed a reduction of saturated and monounsaturated and a relative increase of polyunsaturated fatty acid content of platelet phospholipids. A selective relative increase was observed of some n-3 polyunsaturated fatty acids like eicosapentaenoic and docosahexaenoic acid whereas arachidonic acid decreased. The present study indicates a favourable influence of pantethine not only on plasma but also on platelet lipids which could be of value in delaying the development of atherosclerosis in dyslipidaemic patients. Gensini GF, Prisco D, Rogasi PG, Matucci M, Neri Serneri GG. Int J Clin Pharmacol Res 1985;5(5):309-18

PMID: 4066081 [PubMed - indexed for MEDLINE]

Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age

Servizio di Cardiologia, Istitut Clinici di Perfezionamento, Milano.

Cardiovascular diseases are the main cause of death also in women. Their incidence, rapidly growing in the peri-menopausal period, is related to serum levels of total cholesterol and its LDL fraction. It was also shown that the peroxidation of LDL is an additional factor in the genesis of atherosclerotic vascular disease. As long-term treatments with synthetic lipid-lowering drugs may cause undesirable side effects, while pantethine is known to be well tolerated, we treated 24 hypercholesterolemic women (total serum cholesterol greater than or equal to 240 mg/dl), in perimenopausal age (range: 45-55 years, mean +/- SD = 51.6 +/- 2.4) with 900 mg/day of pantethine. This is a precursor of coenzyme A, with an antiperoxidation effect in vivo, and our aim was to confirm its lipid lowering activity in this particular type of patients. After 16 weeks of treatment, significant reductions of total cholesterol, LDL-cholesterol and LDL-C/HDL-C ratio could be observed. No remarkable changes of the main laboratory parameters (fasting blood sugar, B.U.N., creatinine, uric acid) were seen. Efficacy percentages of the treatment were about 80%. None of the patients complained of adverse reactions due to the treatment with pantethine. In conclusion, we suggest that pantethine should be considered in the long-term treatment of lipid derangements occurring in the perimenopausal age. Binaghi P, Cellina G, Lo Cicero G, Bruschi F, Porcaro E, Penotti M. Minerva Med 1990 Jun;81(6):475-9

PMID: 2359503 [PubMed - indexed for MEDLINE]

Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children.

Following a brief outline of current knowledge concerning atherosclerosis and its treatment, the authors describe the results obtained by treating with pantethine (900-1200 mg daily for 3 to 6 months) a series of 7 children and 65 adults suffering from hypercholesterolemia alone or associated with hypertriglyceridemia (types IIa and IIb of Fredrickson's classification). Pantethine treatment produced significant reduction of the better known risk factors (total cholesterol, LDL-cholesterol, triglycerides, and apo-B) and a significant increase of HDL-cholesterol (signally HDL2) and apolipoprotein A-I. The authors conclude with a discussion of these results and of the possible role of pantethine in the treatment of hyperlipoproteinemia, in view of its perfect tolerability and demonstrated therapeutic effectiveness. Bertolini S, Donati C, Elicio N, Daga A, Cuzzolaro S, Marcenaro A, Saturnino M, Balestreri R. Int J Clin Pharmacol Ther Toxicol 1986 Nov;24(11):630-7

PMID: 3098691 [PubMed - indexed for MEDLINE]

Clinical use of pantethine by parenteral route in the treatment of hyperlipidemia

Servizio di Malattie del Ricambio e Diabetologia, Ospedali Riuniti, Parma.

Recent investigations have confirmed the effectiveness and the excellent tolerability of pantethine, a derivative of pantetheine, an essential part of the acetylation coenzyme CoA, administered P.O., in normalizing the blood lipid concentrations of patients with hyperlipidemias. A group of 18 patients with hyperlipidemias (9 M, 9 F), with an average age of 52.6 years, was submitted to pantethine parenteral treatment. After a 20 days wash-out, pantethine (400 mg/day; BID) was administered intramuscularly, for 20 days. Total cholesterol, triglycerides, HDL-cholesterol, apo A-1 and B lipoprotein, uric acid in serum, glycemia, CBC, B.U.N., creatininemia, E.S.R., SGOT, SGPT, bilirubinemia, cardiac frequency, blood pressure and body weight were controlled before and after treatment. The drug showed to have a therapeutic effectiveness by a rapid and significant improvement in the blood lipid pattern with reduction of total cholesterol, triglycerides and apo-B lipoprotein and increase of HDL-cholesterol and apo A-1 lipoprotein. The tolerability of pantethine at the stated dosage and mode of administration was invariably excellent, with non complaints or visible side effects imputable to the test drug. BUN, creatininemia, glycemia, SGOT, SGPT, bilirubinemia, E.S.R., CBC, cardiac frequency and blood pressure readings showed no noteworthy changes throughout the study. Arsenio L, Bodria P, Bossi S, Lateana M, Strata A. Acta Biomed Ateneo Parmense 1987;58(5-6):143-52

PMID: 2970754 [PubMed - indexed for MEDLINE]

Effect of pantethine on cholesterol ester metabolism in rat arterial wall.

The total serum cholesterol level in rats fed on a high cholesterol diet (HCD) for 16 weeks was markedly higher than that in rats fed on a normal diet (ND), but pantethine reduced the increased level in rats fed on HCD (P less than 0.05). Acid cholesterol esterase activity (acid CEase) of arterial wall homogenates from rats fed on HCD was significantly lower than that of rats fed on ND (P less than 0.005). Acid CEase activity in the arterial wall of rats fed on HCD for 8 weeks and then ND for 8 weeks was less than that of rats fed on ND for 16 weeks. Acid CEase activity in the arterial wall was increased in rats fed on pantethine-containing diet. The ratio of cholesterol ester synthesizing activity to neutral cholesterol esterase (neutral CEase) activity was higher in rats fed on NCD than in those fed on ND. The ratio was lower in rats on the pantethine-containing diet than in those on NCD. The relationship between hypercholesterolemia and lipid metabolism in the arterial wall and effects of pantethine are discussed on the basis of these results. Shinomiya M, Matsuoka N, Shirai K, Morisaki N, Sasaki N, Murano S, Saito Y, Kumagai A. Atherosclerosis 1980 May;36(1):75-80

PMID: 7387778 [PubMed - indexed for MEDLINE]

Effect of pantethine on lipoprotein profiles and HDL subfractions in experimentally hypercholesterolemic rabbits.

A high-cholesterol diet caused in rabbits a great increase in beta-migrating VLDL and a significant decrease in HDL 2 (43% of normal) and HDL 3 masses (64% of normal), without significant changes in HDL cholesterol values. Chemical analysis of the HDL subfractions indicated an abnormal lipid-protein composition in the hypercholesterolemic rabbits, an increase in cholesterol and a decrease in the contents of triglycerides and phospholipid. When these rabbits were treated for about 1 month with pantethine, and intermediate precursor of coenzyme A, the increase in cholesterol levels was effectively prevented in the beta-VLDL (11%) and LDL fractions (43%) but, conversely, HDL-cholesterol was significantly increased (151%). In a separate experiment, HDL 2 and HDL 3 masses were calculated to be increased to 186% and 193%, respectively, by pantethine treatment, when compared with those in control cholesterol-fed rabbits. Serum apolipoprotein AI antigen levels were also significantly increased by the treatment. Tomikawa M, Nakayasu T, Tawara K, Kameda KY, Abiko Y. Atherosclerosis 1982 Feb;41(2-3):267-77

PMID: 7066075 [PubMed - indexed for MEDLINE]

Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia.

Pantethine (P), the stable disulphate form of pantetheine, major component and precursor of coenzyme A, was evaluated within a double-blind protocol (8 weeks for P or for a corresponding placebo) in 29 patients, 11 with type IIB hyperlipoproteinemia, 15 with type IV, and 3 with an isolated reduction of high density lipoprotein cholesterol (HDL-C) levels. In type IIB patients, P (300 mg t.i.d.) determined a highly significant lowering of plasma total and low density lipoprotein (LDL) associated cholesterol (-13.5% for both parameters). In the same patients, HDL-C levels increased about 10% at the end of treatment. Switching from P to placebo was associated with a rapid return to the baseline cholesterolemia. Both in type IIB and type IV patients, plasma triglyceride levels were reduced around 30%, when P was given as the first treatment; when it was preceded by placebo, reductions were less striking (respectively, -17.8% for type IIB and -13.0% for type IV, at the end of P treatment). HDL-C levels were not increased by P, either in type IV, and in the patients with low HDL cholesterolemia. In type IV, LDL cholesterol levels showed a variable response to P: they tended to increase when below 132 mg/dl, prior to treatment, and to be reduced when above this level. This study provides evidence for a significant hypocholesterolemic effect of P, a natural compound free of overt side effects. It also indicates that P may raise HDL-C levels in type IIB patients, while moderately reducing triglyceridemia. Gaddi A, Descovich GC, Noseda G, Fragiacomo C, Colombo L, Craveri A, Montanari G, Sirtori CR. Atherosclerosis 1984 Jan;50(1):73-83

PMID: 6365107 [PubMed - indexed for MEDLINE]

Lowering effect of pantethine on plasma beta-thromboglobulin and lipids in diabetes mellitus.

Second Department of Internal Medicine, Asahikawa Medical College, Japan.

Pantethine in a dosage of 600 mg for the first 3 months, and in a dosage of 1200 mg for the second 6 months was given to 16 diabetics in whom plasma beta-thromboglobulin was raised (greater than 50 ng/ml). Plasma beta-TG levels decreased significantly with pantethine treatment for 9 months. Plasma triglyceride, total cholesterol, apo E and apo CII levels decreased significantly after 9 months. Plasma LDL-C and atherogenic index (LDL-C/HDL-C ratio or apo B/apo AI ratio) tended to decrease with treatment. It is concluded that administration of pantethine may be beneficial in the prevention of diabetic angiopathy because of its lowering effect on plasma beta-TG, lipids and apolipoproteins. Eto M, Watanabe K, Chonan N, Ishii K. Artery 1987;15(1):1-12

PMID: 2963604 [PubMed - indexed for MEDLINE]

Effects of pantethine on cholesterol synthesis from mevalonate in isolated rat hepatocytes.

Results presented here show that when isolated rat hepatocytes are incubated with increasing concentrations of [2-14C]mevalonolactone, incorporation of the substrate into cholesterol is progressively reduced. Correspondingly, an increase of the incorporation of the substrate into precursors of cholesterol (methyl sterols and squalene) occurs. These effects and the observed inhibition of HMGCoA reductase at high mevalonolactone concentration (0.5 mM) are in agreement with those shown by others in cultured hepatocytes. Since pantethine was reported to affect cholesterol biosynthesis from mevalonate in cultured fibroblasts, effects of its addition to hepatocyte incubations at low and high mevalonolactone concentration were studied. Neither the amount of radioactivity incorporated into cholesterol and in its sterol precursors nor sterol levels were modified by pantethine when a mevalonolactone concentration (0.01 mM) that did not alter the levels of intermediates of cholesterol synthesis was used. Pantethine was shown instead to potentiate the decrease of mevalonate incorporation into cholesterol induced by high concentrations of mevalonolactone (0.5 mM). Decrease of 3-hydroxy-3-methylglutaryl CoA reductase activity induced by 1 mM pantethine was twice that caused by mevalonolactone alone. These results may explain the fact that both in laboratory animals and in humans pantethine administration is effective in reducing cholesterol plasma levels in hyperlipidemic conditions. Cighetti G, Del Puppo M, Paroni R, Galli G, Kienle MG. Atherosclerosis 1986 Apr;60(1):67-77

PMID: 3707674 [PubMed - indexed for MEDLINE]

Pantethine reduces plasma cholesterol and the severity of arterial lesions in experimental hypercholesterolemic rabbits.

Pantethine (P), a coenzyme A precursor, was administered to cholesterol-fed rabbits (0.5% cholesterol diet + 1% pantethine) for 90 days. At the end of treatment, plasma total cholesterol levels were reduced 64.7% and the HDL/total cholesterol ratio increased in P-treated animals; a significant rise of the apo A-I/A-II ratio was detected in HDL. VLDL lipid and protein levels were, on the other hand, reduced by P. The cholesterol-ester content of both liver and aortic tissues was not significantly affected by P. Although the total aortic area with evident plaques was reduced only 18.2%, the microscopical examination of sections from the major vessels of P-treated animals, showed a reduction in the severity of lesions, both in the aorta and in the coronary arteries. These findings suggest that P, in addition to significantly lowering plasma cholesterol levels in rabbits on an experimental diet, may modify lipid deposition in major arteries, possibly by affecting lipoprotein composition and/or exerting an arterial protective effect. Carrara P, Matturri L, Galbussera M, Lovati MR, Franceschini G, Sirtori CR. Atherosclerosis 1984 Dec;53(3):255-64

PMID: 6442152 [PubMed - indexed for MEDLINE]

Comparison of the efficacy of pantethine, acipimox, and bezafibrate on plasma lipids and index of cardiovascular risk in diabetics with dyslipidemia]

Servizio di Diabetologia, Ospedale Civile, Udine.

Atherosclerotic manifestations are more common and precocious in diabetics than in the general population. Due to the increased cardiovascular risk, a primary or secondary (to diabetes mellitus) lipoprotein disorder in diabetics has to be carefully considered. 27 diabetics (15 NIDDM and 12 IDDM) with dyslipidemia (14 type IV, 8 type IIa and 5 type IIb) were divided in 3 groups and treated with 3 different hypolipemic drugs (Group A: pantethine 600 mg/day; Group B: acipimox 500 mg/day; Group C: bezafibrate 600 mg/day) to test their efficacy and acceptancy. Body weight, Hb A1-c, serum lipoproteins have been measured before and during the 6 months treatment. A significant variation of lipidemic pattern was observed in Group C: a decrease of cholesterol (-20%), triglycerides (-40%), LDL (-24.4%) and apo B (-26.8%) with an increase of HDL (+23.6%). Pantethine and acipimox were more effective on triglycerides (-37.7% and -23.3% respectively). Cardiovascular risk (CT tot/CT HDL) was significantly reduced with acipimox and normalized with bezafibrate. Tonutti L, Taboga C, Noacco C. Minerva Med 1991 Oct;82(10):657-63

PMID: 1745376 [PubMed - indexed for MEDLINE]

Investigation of the roles of the substances in serum lipids and their constitutive fatty acids in chronic urticaria.

The newly-generated lipid mediators include products of arachidonate metabolism, prostaglandins and leukotrienes. In this study, serum lipids and fatty acids, including arachidonic acid (C20:4) were examined in 12 normal subjects (6 males and 6 females) and 23 subjects with chronic urticaria (6 males and 17 females), including 17 who made an excellent or good recovery (4 males and 13 females). The results indicated a relationship between chronic urticaria and serum lipids and fatty acids. The omega 6 (n-6) and omega 3 (n-3) series of polyunsaturated fatty acids and lipid peroxidation were suggested that may be one of the mediators in chronic urticaria. Pantethine, glutathione and ascorbic acid were effective in controlling chronic urticaria. J Dermatol 1989 Jun;16(3):196-206 Kobayashi S.

PMID: 2794222 [PubMed - indexed for MEDLINE]

Pantethine, diabetes mellitus and atherosclerosis. Clinical study of 1045 patients

After a review of the clinical studies on the treatment of diabetic patients with pantethine, the authors discuss the results obtained in a postmarketing surveillance (PMS) study on 1045 hyperlipidemic patients receiving pantethine (900 mg/day on average). Of these patients, 57 were insulin-dependent (Type I) and 241 were non insulin-dependent (Type II) diabetics. Beyond the epidemiological considerations made possible by a PMS study, the authors show that pantethine brought about a statistically significant and comparable improvement of lipid metabolism in the three groups of patients, with very good tolerability. Pantethine should therefore be considered for the treatment of lipid abnormalities also in patients at risk such as those with diabetes mellitus. Donati C, Bertieri RS, Barbi G. Clin Ter 1989 Mar 31;128(6):411-22

PMID: 2524328 [PubMed - indexed for MEDLINE]

Therapeutic efficacy of pantothenic acid preparations in ischemic heart disease patients

The therapeutic effectiveness of the pantothenic acid drugs: calciipantothenas and pantethine, was studied in 182 patients with coronary heart disease and stable angina of effort. It is shown that both the drugs produce favourable effects on certain parameters of hemodynamics, on the metabolism of lipids, riboflavin and ascorbic acid. It is recommended that the administration of calciipantothenas in a dose of 300 mg/day, during 3 weeks, be included into the combined treatment of coronary patients with no manifest disorders of lipid metabolism. Patients with manifest hyperlipidemia should be administered pantethine in a dose of 500 mg/day. Borets VM, Lis MA, Pyrochkin VM, Kishkovich VP, Butkevich ND. Vopr Pitan 1987 Mar-Apr;(2):15-7

PMID: 3590676 [PubMed - indexed for MEDLINE]

Hyperlipidemia, diabetes and atherosclerosis: efficacy of treatment with pantethine

The hypolipidemizing effects of Pantethine were investigated by the Authors in 37 hypercholesterolemic and/or hypertriglyceridemic patients. Of these, 21 were also diabetic, in a satisfying glucidic compensation, in order to verify the action of this drug also in this metabolic condition. The study was carried out for three months and during this period the patients were given Pantethine at the dose of 600 mg/die orally. At the 30th, the 60th, the 90th day of treatment the following parameters were controlled: cholesterolemia, HDL cholesterol, apolipoproteins A and B, triglyceridemia, systolic and diastolic arterial pressure, uricemia, body weight. Thirty days after suspending the treatment, the parameters were controlled again to detect a possible "rebound" effect. The results were analyzed on the whole case-record, subdividing the patients in dislipidemic and diabetic-dislipidemic, and on the basis of the Fredrickson's classification. Pantethine induced in all groups a quick and progressive decrease of cholesterolemia, triglyceridemia, LDL cholesterol and Apolipoproteins B with increased HDL cholesterol and Apolipoproteins A. After suspending the treatment, there is a clear inversion of the state of these parameters. The Authors conclude that the present work shows that Pantethine, a natural and atoxic substance, an important component of Coenzyme A, is efficacious in determining a clear tendency towards normalization of the lipidic values. Arsenio L, Caronna S, Lateana M, Magnati G, Strata A, Zammarchi G. Acta Biomed Ateneo Parmense 1984;55(1):25-42

PMID: 6232801 [PubMed - indexed for MEDLINE]

Effectiveness of long-term treatment with pantethine in patients with dyslipidemia.

A one-year clinical trial with pantethine was conducted in 24 patients with established dyslipidemia of Fredrickson's types II A, II B, and IV, alone or associated with diabetes mellitus. The treatment was well tolerated by all patients with no subjective complaints or detectable side effects. Blood lipid assays repeated after 1, 3, 6, 9, and 12 months of treatment revealed consistent and statistically significant reductions of all atherogenic lipid fractions (total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B) with parallel increases of high-density lipoprotein cholesterol and apolipoprotein A. The results were equally good in patients with uncomplicated dyslipidemia and in those with associated diabetes mellitus. The authors conclude that pantethine (a drug entity related to the natural compound, pantetheine) represents a valid therapeutic support for patients with dyslipidemia not amenable to satisfactory correction of blood lipids by diet alone. Arsenio L, Bodria P, Magnati G, Strata A, Trovato R. Clin Ther 1986;8(5):537-45

PMID: 3094958 [PubMed - indexed for MEDLINE]

Pantethine improves the lipid abnormalities of chronic hemodialysis patients: results of a multicenter clinical trial.

In the course of a post-marketing surveillance program on the effectiveness and tolerability of pantethine in the treatment of hyperlipidemia, the effects of the drug were explored in 31 patients with dyslipidemia undergoing chronic hemodialysis. The mean duration of treatment was 9 months (min. 7 months, max. 24 months), with oral doses of 600 to 1200 mg of pantethine daily (mean daily dosage 970 mg). Improvement was noted in terms of total blood cholesterol in the 7 patients with basal hypercholesterolemia (p less than 0.01) and highly significant reduction of serum triglycerides. No variations of HDL-cholesterol or total Apo-A were detected. None of the patients experienced any adverse effects from the treatment. In the light of extensive experience with the drug, plus the results of this study, the authors conclude by stressing the importance of an effective and readily tolerated product, such as pantethine, for the treatment of dyslipidemia in patients on chronic hemodialysis. Donati C, Barbi G, Cairo G, Prati GF, Degli Esposti E. Clin Nephrol 1986 Feb;25(2):70-4

PMID: 3516477 [PubMed - indexed for MEDLINE]