Mitochondrial myopathy ?A result of clofibrate/etofibrate treatment?

Bardosi, A.; Scheidt, Peter C.; Goebel, Hans‐Hilmar

doi:10.1007/bf00688640

Cited by 15 publications

(7 citation statements)

References 14 publications

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“…Statins inhibit the HMG-CoA-reductase resulting in lower intracellular cholesterol levels.This later is an important component of cell membranes modulating their fluidity [1][2][3][4][5] . Myotoxicity associated to the use of statin is complex, involving mechanisms on the structure and function of the cellular membrane, mitochondrial dysfunction, and changes in the duplication of the myocyte [1][2][3][4][5][6][7][8][13][14][15] . A reduction in plasmatic and intracellular cholesterol can result in reduced levels of the membrane cholesterol leading to physical changes in this and a decrease in cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that in the various manifestations of toxic myopathies, the vacuolar and mitochondrial changes are usually painless, and with raised CK 13 as seen in cases 1,2,5, and 6, or even normal CK 12 . In cases with rapid onset, muscular pain tends to predominate 13 , however weakness in proximal musculature predominated in two of our cases (cases 2 and 8).…”

Section: Discussionmentioning

confidence: 99%

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Statin and fibrate associed myopathy: study of eight patients

Carvalho

Lima

Valiente

2004

Arq. Neuro-Psiquiatr.

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-Lipid-lowering drugs have been occasionally associated with neuromuscular symptoms and muscle biopsy changes. We reported the clinical course and the muscle biopsy in eight patients with hyperlipoproteinemia, treated with lipid -lowering drugs (statins/fibrates). Five patients had myalgias while; in two cases there was proximal muscle weakness. All patients became asymptomatic after the withdrawal of the drug, although creatine kinase remained elevated. We performed muscle biopsy in six cases from three months to two years after suspension of the drug. We found variation in fibers diameters in all cases, with necrosis of fibers in five cases, inflammatory infiltration in one case, the presence of vacuolated fiber in one patient and ragged-red fibers in three subjects. We concluded that although the muscle biopsy findings were not specific, the prolonged use of statins and or fibrates might induce a chronic myopathy even in the absence of symptoms.KEY WORDS: statins, fibrates, myopathy, muscle biopsy, creatine kinase. Miopatia associada a estatina e fibrato: estudo de oito pacientesRESUMO -As drogas redutoras de colesterol são ocasionalmente associadas a sintomas neuromusculares e alterações morfológ-icas observadas na biopsia muscular. Relatamos o curso clínico e achado da biopsia muscular em oito pacientes com hiperlipoproteinemia tratados com drogas redutoras de colesterol (estatinas/fibratos). Cinco pacientes tiveram mialgia e em dois havia fraqueza muscular proximal.Todos os pacientes ficaram assintomáticos após retirada da medicação embora a creatinoquinase permanecesse elevada. Analisamos a biopsia muscular em seis casos realizados entre três meses e dois anos após a suspensão da droga. Encontramos variação no calibre das fibras em todos os casos com necrose de fibras em cinco, infiltrado inflamatório em um caso, presença de vacúolos em um e "ragged red fiber" em três deles. Concluímos que, embora os achados da biopsia muscular não fossem específicos, o uso prolongado de estatinas e/ou fibratos pode induzir a uma miopatia crônica até mesmo na ausência de sintomas.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Statin and fibrate associed myopathy: study of eight patients

Carvalho

Lima

Valiente

2004

Arq. Neuro-Psiquiatr.

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“…The main clinical related myopathies [ 11]. Statins inhibit synthesis of mevalonate, a precursor of adverse effects of statins are muscular and include elevation of serum creatine kinase, sometimes associated both cholesterol and ubiquinone.…”

Section: Introductionmentioning

confidence: 99%

“…syndromes related to fibrate therapy have mentioned mitochondrial abnormalities in muscle [11,31 ]. The hypothesis of a mitochondrial dysfunction induced by Ubiquinone determinations fibrate therapy still needs to be substantiated.…”

Section: Introductionmentioning

confidence: 99%

Lipid‐lowering drugs and mitochondrial function: effects of HMG‐CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio

Pinieux¹,

Chariot

Ammi-Saı̈d³

et al. 1996

Brit J Clinical Pharma

246

125

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1 Statins inhibit synthesis of mevalonate, a precursor of ubiquinone that is a central compound of the mitochondrial respiratory chain. The main adverse effect of statins is a toxic myopathy possibly related to mitochondrial dysfunction. 2 This study was designed to evaluate the effect of lipid-lowering drugs on ubiquinone (coenzyme Q10 ) serum level and on mitochondrial function assessed by blood lactate/pyruvate ratio. 3 Eighty hypercholesterolaemic patients (40 treated by statins, 20 treated by fibrates, and 20 untreated patients, all 80 having total cholesterol levels >6.0 mmol l−1) and 20 healthy controls were included. Ubiquinone serum level and blood lactate/pyruvate ratio used as a test for mitochondrial dysfunction were evaluated in all subjects. 4 Lactate/pyruvate ratios were significantly higher in patients treated by statins than in untreated hypercholesterolaemic patients or in healthy controls (P<0.05 and P<0.001). The difference was not significant between fibratetreated patients and untreated patients. 5 Ubiquinone serum levels were lower in statin-treated patients (0.75 mg l−1±0.04) than in untreated hypercholesterolaemic patients ( 0.95 mg l−1±0.09; P<0.05). 6 We conclude that statin therapy can be associated with high blood lactate/ pyruvate ratio suggestive of mitochondrial dysfunction. It is uncertain to what extent low serum levels of ubiquinone could explain the mitochondrial dysfunction.

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“…1991 Accepted: Februar. 10,1992 id-lowering agent, bezafibrate, a clofibrate analog. This syndrome occurred in subjects with normal as well as impaired kidney function [5,6], Pharmacokinetic investi gations of bezafibrate in patients with chronic uremia showed that the half-life is significantly prolonged and renal clearance is markedly decreased [7], On the basis of these data, a dose adjustment has been suggested in patients with renal impairment.…”

Section: Introductionmentioning

confidence: 99%

Bezafibrate-Induced Myopathy: No Evidence for Defects in Muscle Metabolism

Vita

Toscano

Mileto³

et al. 1993

Eur Neurol

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A 58-year-old man with chronic renal failure developed severe muscle pain and tenderness 1 week after starting bezafibrate 400 mg daily. Serum creatine kinase was 32,280 U/l. Muscle biopsy revealed scattered necrotic fibers and mild type 2b atrophy. Muscle total and free carnitine were at the upper limits of the normal range. Biochemical investigations of muscle homogenate showed normal carnitine pelmityl transferase (CPT) as well as normal individual glycolytic and mitochondrial enzyme activities. Withdrawal of the drug was followed by rapid clinical improvement. Our study casts doubt on the hypothesis that bezafibrate is able to affect muscle metabolic pathways. It is likely that the drug acts on cholesterol constituents of the muscle membrane, producing discontinuities of the sarcolemma and initiating cell necrosis.

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Mitochondrial myopathy ?A result of clofibrate/etofibrate treatment?

Cited by 15 publications

References 14 publications

Statin and fibrate associed myopathy: study of eight patients

Statin and fibrate associed myopathy: study of eight patients

Lipid‐lowering drugs and mitochondrial function: effects of HMG‐CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio

Bezafibrate-Induced Myopathy: No Evidence for Defects in Muscle Metabolism

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