cerivastatin and Muscular-Diseases

Numerous studies have illustrated the relationship between SLCO1B1 T521C polymorphism and statin-induced myopathy risk; however, this association is not consistent. Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from inception to October 2017 to identify potential studies. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from different genetic models by using a random-effects model. Fourteen studies comprising 3265 myopathy patients and 7743 controls were included. The summary ORs suggested that 521CC (OR: 2.31; 95% CI: 1.15-4.63; P = 0.019), 521TC (OR: 1.34; 95% CI: 1.02-1.76; P = 0.034), and 521CC + TC (OR: 1.82; 95% CI: 1.32-2.51; P < 0.001) were associated with a greater risk of statin-induced myopathy than 521TT. The higher incidence of statin-induced myopathy was found to be significantly correlated with the C allele compared with the T allele (OR: 1.89; 95% CI: 1.36-2.62; P < 0.001). In addition, we observed that 521CC + TC was associated with an increased risk of myopathy in individuals who received simvastatin (OR: 2.35; 95% CI: 1.08-5.12; P = 0.032) or rosuvastatin (OR: 1.69; 95% CI: 1.07-2.67; P = 0.024) when compared with 521TT. The 521C allele was associated with a greater risk of cerivastatin-induced myopathy than the T allele (OR: 1.95; 95% CI: 1.47-2.57; P < 0.001). The findings of this study indicated that SLCO1B1 T521C was associated with a significantly higher risk of statin-induced myopathy, especially for simvastatin, rosuvastatin, and cerivastatin. Future studies should be conducted in subjects receiving specific types of drugs, and any potential adverse events need to be explored.

Topics: Aged; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Male; Middle Aged; Muscular Diseases; Pharmacogenetics; Pharmacogenomic Variants; Polymorphism, Genetic; Pyridines; Risk Assessment; Risk Factors; Rosuvastatin Calcium; Simvastatin

Rosuvastatin is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Although highly efficacious, this new statin has generated considerable controversy regarding its safety. Rosuvastatin was approved for clinical use based on the largest pre-approval database for all statins prior to commercial use. In this database, rosuvastatin had a similar safety profile to other approved statins up to the highest approval dose of 40 mg. As with all statins, there is a marked increase in adverse effects when the dose is titrated from 40 to 80 mg, and rosuvastatin demonstrates a similar dose/toxicity relationship. In the pre-approval data trials on 80 mg, there was a 1.0% (n = 16) incidence of myopathy and 7 patients developed rhabdomyolysis. However the

Topics: Acute Kidney Injury; Adverse Drug Reaction Reporting Systems; Biomarkers; Cholesterol, LDL; Creatine Kinase; Creatine Kinase, MM Form; Drug Approval; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Incidence; Isoenzymes; Kidney Tubules; Muscular Diseases; Product Surveillance, Postmarketing; Proteinuria; Pyridines; Pyrimidines; Rhabdomyolysis; Rosuvastatin Calcium; Sulfonamides

Combination lipid-altering regimens represent an emerging clinical paradigm to meet increasingly stringent consensus lipoprotein targets for coronary prevention. This practice, together with escalating prevalences of coronary artery disease in certain ageing (western industrial) populations, polypharmacy in the elderly and the recent voluntary market withdrawal of cerivastatin, warrants a re-examination of the safety profiles of 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (i.e., statins). These agents are exceedingly well-tolerated in the vast majority of patients, very infrequently precipitating musculoskeletal symptoms and/or signs. Statins vary in their pharmacological profiles, leading to distinct levels of systemic exposure and capacities to penetrate skeletal myocytes. Pharmacokinetic interactions with certain agents increase the likelihood of statin-induced myopathy and, in exceedingly rare instances, potentially fatal rhabdomyolysis with myoglobinuria and renal failure. As with other medical decisions, the anticipated benefits of long-term statin therapy, with or without other lipid-altering agents, need to be weighed against the prospects of clinically significant drug interactions. In clinical trials and postmarketing surveillance, the two statins that are not metabolised by the cytochrome P450 3A4 system (fluvastatin and pravastatin) have exhibited very low propensities to elicit myopathy when combined with other agents. These agents should be considered initially when contemplating combination lipid-lowering regimens for coronary prevention.

Topics: Cytochrome P-450 Enzyme System; Drug Interactions; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Muscular Diseases; Practice Guidelines as Topic; Product Surveillance, Postmarketing; Pyridines; Risk Factors

Significant progress has been made in including women in clinical and drug evaluation trials. Nonetheless, for most drugs currently on the market, analysis of benefits by sex is not available. At least some of the adverse effects of newer drugs in women could be due to the lack of inclusion in studies from which therapeutic regimens were derived. The data currently available on potential sex differences in pharmacokinetics and pharmacodynamics are also limited by having been obtained from healthy subjects receiving only one medication in studies designed only to detect moderate-to-large (> 30-50%) differences between the sexes. The clinical environment is different: patients consume multiple medications, including over-the-counter medications as well as nutraceuticals and dietary supplements; patients are, on average, older than healthy volunteers or even patients enrolled in investigational studies; and patients are more likely to have multiple diseases. In addition, adequate numbers of women still have not been enrolled in clinical trials for the therapy of many common disorders. The prudent clinician will remember that every time a therapy is initiated for an individual patient, especially a female patient, it is a clinical trial and the outcome is uncertain.

Topics: Clinical Trials as Topic; Drug Evaluation, Preclinical; Female; Humans; Mibefradil; Muscular Diseases; National Institutes of Health (U.S.); Practice Guidelines as Topic; Pyridines; Sex Factors; United States; Women; Women's Health

Myopathy occurs in 0.1%-0.2% of patients receiving statins in clinical trials. This adverse effect is shared by all statins, but is more common with cerivastatin, especially in combination with gemfibrozil. The risk of myopathy is increased by: the use of high doses of statins, concurrent use of fibrates, concurrent use of hepatic cytochrome P450 inhibitors, acute viral infections, major trauma, surgery, hypothyroidism and other conditions. Statin-associated myopathy should be suspected when a statin-treated patient complains of unexplained muscle pain, tenderness or weakness. Statin therapy should be stopped in cases of suspected myopathy, and serum creatine kinase levels should be checked and monitored. No specific therapies other than statin withdrawal and supportive measures for rhabdomyolysis are currently available.

Topics: Creatine Kinase; Drug Interactions; Drug Monitoring; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Muscular Diseases; Pyridines

Rhabdomyolysis is a rare but potentially fatal complication associated with the use of cholesterol synthesis inhibitors (statins). The complication can develop in susceptible patients and with the concomitant use of medications that impede the biodegradation of statins, for example, biotransformation via the cytochrome P450 system. This may result in the plasma and tissue concentrations of statins, and their active metabolites, increasing to levels that are toxic for striated muscle. Myopathy is present when plasma activity levels of creatinine kinase are raised to in excess of 10 times the upper limit of the normal value. Muscular complaints which may be indicative of myotoxicity and subsequent myopathy are present in 1-7% of statin users. Albeit to varying degrees, all statins can induce myotoxicity especially at high dosages. Rhabdomyolysis was clearly more prevalent under cerivastatin users than the users of other statins and was therefore recently withdrawn from the market. Statins should be withdrawn immediately if myopathy is suspected. Prompt withdrawal may prevent rhabdomyolysis.

Topics: Creatine Kinase; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug and Narcotic Control; Drug Interactions; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Mixed Function Oxygenases; Muscular Diseases; Netherlands; Pyridines; Rhabdomyolysis

Microphysiological tissue engineering models of human skeletal muscle (myobundles) provide a platform to investigate the mechanism of muscle diseases and to study the response to drugs and toxins in vitro. To examine the dynamic response to drugs, which often take several days to induce responses, we developed a system to monitor the contractile force of the same human skeletal muscle myobundles over time before and after treatment with drugs. Myobundles were formed in series with Ecoflex films (platinum-catalyzed silicones) with embedded microbeads. The displacement of the microbeads in Ecoflex exhibited a linear relation between muscle force production and Ecoflex film stretch. Forces measured with the microbeads embedded in Ecoflex agreed well with simultaneous measurements with a force transducer. Application of the Hill model for the myobundles showed that the Ecoflex affected the magnitude of the response, but not the kinetics. After continuous exposure to 100 nM cerivastatin, both active and passive forces were reduced relative to controls after 2-4 days. The decline in force was associated with a decline in the muscle myofiber organization. The inhibitory effect of cerivastatin was reduced when 0.1-1 mM mevalonate was added with cerivastatin. Although addition of co-enzyme Q10 with cerivastatin inhibited degradation of sarcomeric α-actinin (SAA) in myoblasts, the contractile force still declined, suggesting that statin-induced myopathy was related to mevalonate pathway but the addition of co-enzyme Q10 was insufficient to overcome the effect of statins on the mevalonate pathway. Thus, cerivastatin rapidly induces myopathy which can be reversds with mevalonate but not co-enzyme Q10.

Topics: Biomechanical Phenomena; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Microtechnology; Muscle Contraction; Muscle, Skeletal; Muscular Diseases; Pyridines; Tissue Engineering

To identify new candidate biomarkers for skeletal muscle toxicity, an unbiased metabolomic analysis was performed in rats treated with two distinct myotoxicants, cerivastatin (CER) and tetramethyl-p-phenylenediamine (TMPD). Skeletal muscle toxicity was induced in male Fischer 344 rats by administering CER or TMPD and monitored using established endpoints, such as increased plasma creatine kinase (CK) activity and histopathology, and a metabolomic analysis of skeletal muscle and plasma samples. Plasma CK levels in CER-treated rats were markedly elevated at Day 11; however, those in TMPD-treated rats showed a statistically significant decrease at 24 hr after dosing. Light microscopy revealed that vacuolated or necrotic fibers were evident in all CER-treated rats on Day 11, and slightly vacuolated fibers were observed in TMPD-treated rats at 6 and 24 hr after dosing. Metabolomic analysis of the rectus femoris indicated increases in 2-hydroxyglutarate (2HG) in CER-treated rats and hexanoylcarnitine in CER- and TMPD-treated rats. There were also increases in plasma 2HG in CER-treated rats on Days 8 and 11 and in TMPD-treated rats at 24 hr after dosing and increases in plasma hexanoylcarnitine in CER-treated rats on Day 11 and in TMPD-treated rats at 6 and 24 hr after dosing. These experiments demonstrated the potential of plasma 2HG and hexanoylcarnitine as specific and easily detectable biomarkers for skeletal muscle toxicity in rats and demonstrated the value of metabolomics for biomarker detection and identification in toxicological studies.

Topics: Aniline Compounds; Animals; Biomarkers; Carnitine; Creatine Kinase; Disease Models, Animal; Glutarates; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Pyridines; Rats, Inbred F344

Patients with self-limited statin-related myopathy improve spontaneously when statins are stopped. In contrast, patients with statin-associated autoimmune myopathy have autoantibodies recognizing 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and usually require immunosuppressive therapy to control their disease. On initial presentation, it can sometimes be difficult to distinguish between these 2 diseases, as both present with muscle pain, weakness, and elevated serum creatine kinase (CK) levels. The goal of this study was to determine whether patients with severe self-limited statin-related myopathy also make anti-HMGCR autoantibodies.. We screened 101 subjects with severe self-limited cerivastatin-related myopathy for anti-HMGCR autoantibodies.. No patient with severe self-limited cerivastatin-related myopathy had anti-HMGCR autoantibodies.. Anti-HMGCR autoantibody testing can be used to help differentiate whether a patient has self-limited myopathy due to cerivastatin or autoimmune statin-associated myopathy; these findings may apply to other statins as well. Muscle Nerve 54: 142-144, 2016.

Topics: Aged; Autoantibodies; Creatine Kinase; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Muscular Diseases; Pyridines; Retrospective Studies

Nuclear magnetic resonance (NMR)-based metabolomic profiling identified urinary 1- and 3-methylhistidine (1- and 3-MH) as potential biomarkers of skeletal muscle toxicity in Sprague-Dawley rats following 7 and 14 daily doses of 0.5 or 1mg/kg cerivastatin. These metabolites were highly correlated to sex-, dose- and time-dependent development of cerivastatin-induced myotoxicity. Subsequently, the distribution and concentration of 1- and 3-MH were quantified in 18 tissues by gas chromatography-mass spectrometry. The methylhistidine isomers were most abundant in skeletal muscle with no fiber or sex differences observed; however, 3-MH was also present in cardiac and smooth muscle. In a second study, rats receiving 14 daily doses of 1mg/kg cerivastatin (a myotoxic dose) had 6- and 2-fold elevations in 1- and 3-MH in urine and had 11- and 3-fold increases in 1- and 3-MH in serum, respectively. Selectivity of these potential biomarkers was tested by dosing rats with the cardiotoxicant isoproterenol (0.5mg/kg), and a 2-fold decrease in urinary 1- and 3-MH was observed and attributed to the anabolic effect on skeletal muscle. These findings indicate that 1- and 3-MH may be useful urine and serum biomarkers of drug-induced skeletal muscle toxicity and hypertrophy in the rat, and further investigation into their use and limitations is warranted.

Topics: Animals; Biomarkers; Creatine; Dose-Response Relationship, Drug; Female; Magnetic Resonance Spectroscopy; Male; Metabolomics; Methylhistidines; Muscle, Skeletal; Muscular Diseases; Pyridines; Rats; Rats, Sprague-Dawley; Time Factors

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are associated with adverse skeletal muscle toxicity, but the underlying mechanism remains unclear. To investigate the pathological mechanism of statin-induced myotoxicity, cerivastatin (20 ppm; corresponding to 2 mg/kg/day) was dietarily administered to young male F344 rats for 10 days, and time-course clinical observations, measurement of plasma creatine kinase activity, and light and electron microscopy of type I fiber-predominant skeletal muscle (soleus) or type II fiber-predominant skeletal muscles (extensor digitorum longus and tibialis anterior), were performed. Clinical symptoms including weakness of hind limbs, staggering gait and body weight loss, accompanied by marked plasma creatinine kinase elevation in rats fed cerivastatin at around Day 6 to 8. Interestingly, microscopic examination revealed that cerivastatin-induced muscle damages characterized by hypercontraction (opaque) and necrosis of the fibers were of particular abundance in the soleus muscle at Day 8, whereas these histological lesions in the extensor digitorum longus and tibialis anterior were negligible, even at Day 9. Prior to manifestation of muscle damage, swollen mitochondria and autophagic vacuoles in the soleus were observed as the earliest ultra structural changes at Day 6; then activated lysosomes, disarray of myofibril and dilated sarcoplasmic reticulum vesicles became ubiquitous at Day 8. These results demonstrate that cerivastatin induces type I fiber-predominant muscles injury, which is associated with mitochondrial damage, in young male F344 rats. Since the rat exhibiting type I fiber-targeted injury is a unique animal model for statin-induced myotoxicity, it will be useful for gaining insight into mechanisms of statin-induced myotoxicity.

Topics: Aging; Animals; Body Weight; Creatine Kinase; Dose-Response Relationship, Drug; Eating; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Microscopy, Electron, Transmission; Mitochondrial Swelling; Muscle Fibers, Skeletal; Muscular Diseases; Pyridines; Rats; Rats, Inbred F344; Time Factors

Rare instances of myopathy are associated with all statins, but cerivastatin was withdrawn from clinical use due to a greater incidence of myopathy. The mechanism of statin-induced myopathy with respect to tissue disposition was investigated by measuring the systemic, hepatic, and skeletal muscle exposure of cerivastatin, rosuvastatin, and simvastatin in rats before and after muscle damage. The development of myopathy was not associated with the accumulation of statins in skeletal muscle. For each statin exposure was equivalent in muscles irrespective of their fibre-type sensitivity to myopathy. The low amount of each statin in skeletal muscle relative to the liver does not support a significant role for transporters in the disposition of statins in skeletal muscle. Finally, the concentration of cerivastatin necessary to cause necrosis in skeletal muscle was considerably lower than rosuvastatin or simvastatin, supporting the concept cerivastatin is intrinsically more myotoxic than other statins.

Topics: Animals; Disease Models, Animal; Female; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver; Muscle, Skeletal; Muscular Diseases; Pyridines; Pyrimidines; Rats; Rats, Wistar; Rosuvastatin Calcium; Simvastatin; Sulfonamides

Topics: Aged; Alleles; Creatine Kinase; DNA; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Metabolic Diseases; Middle Aged; Muscular Diseases; Mutation; Neurologic Examination; Pravastatin; Protein Prenylation; Pyridines

High-dose statin treatment has been recommended as a primary strategy for aggressive reduction of LDL cholesterol levels and protection against coronary artery disease. The effectiveness of high-dose statins may be limited by their potential for myotoxic side effects. There is currently little known about the molecular mechanisms of statin-induced myotoxicity. Previously we showed that T-91485, an active metabolite of the squalene synthase inhibitor lapaquistat acetate (lapaquistat: a previous name is TAK-475), attenuated statin-induced cytotoxicity in human skeletal muscle cells [Nishimoto, T., Tozawa, R., Amano, Y., Wada, T., Imura, Y., Sugiyama, Y., 2003a. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A. Biochem. Pharmacol. 66, 2133-2139]. In the current study, we investigated the effects of lapaquistat administration on statin-induced myotoxicity in vivo. Guinea pigs were treated with either high-dose cerivastatin (1 mg/kg) or cerivastatin together with lapaquistat (30 mg/kg) for 14 days. Treatment with cerivastatin alone decreased plasma cholesterol levels by 45% and increased creatine kinase (CK) levels by more than 10-fold (a marker of myotoxicity). The plasma CK levels positively correlated with the severity of skeletal muscle lesions as assessed by histopathology. Co-administration of lapaquistat almost completely prevented the cerivastatin-induced myotoxicity. Administration of mevalonolactone (100 mg/kg b.i.d.) prevented the cerivastatin-induced myotoxicity, confirming that this effect is directly related to HMG-CoA reductase inhibition. These results strongly suggest that cerivastatin-induced myotoxicity is due to depletion of mevalonate derived isoprenoids. In addition, squalene synthase inhibition could potentially be used clinically to prevent statin-induced myopathy.

Topics: Animals; Biomarkers; Cholesterol; Creatine Kinase; Drug Antagonism; Drug Therapy, Combination; Enzyme Inhibitors; Farnesyl-Diphosphate Farnesyltransferase; Guinea Pigs; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mevalonic Acid; Muscle, Skeletal; Muscular Diseases; Oxazepines; Piperidines; Pyridines

Topics: Cardiovascular Diseases; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Pain; Pyridines; Pyrimidines; Rosuvastatin Calcium; Sulfonamides

As a class, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors can potentially cause skeletal myopathy. One statin, cerivastatin, has recently been withdrawn from the market due to an unacceptably high incidence of rhabdomyolysis. The mechanism underlying statin-induced myopathy is unknown. This paper sought to investigate the relationship among statin-induced myopathy, mitochondrial function, and muscle ubiquinone levels. Rats were administered cerivastatin at 0.1, 0.5, and 1.0 (mg/kg)/day or dose vehicle (controls) by oral gavage for 15 days. Samples of type I-predominant skeletal muscle (soleus) and type II-predominant skeletal muscle [quadriceps and extensor digitorum longus (EDL)], and blood were collected on study days 5, 10, and 15 for morphological evaluation, clinical chemistry, mitochondrial function tests, and analysis of ubiquinone levels. No histological changes were observed in any of the animals on study days 5 or 10, but on study day 15, mid- and high-dose animals had necrosis and inflammation in type II skeletal muscle. Elevated creatine kinase (CK) levels in blood (a clinical marker of myopathy) correlated with the histopathological diagnosis of myopathy. Ultrastructural characterization of skeletal muscle revealed disruption of the sarcomere and altered mitochondria only in myofibers with degeneration, while adjacent myofibers were unaffected and had normal mitochondria. Thus, mitochondrial effects appeared not to precede myofiber degeneration. Mean coenzyme Q9 (CoQ9) levels in all dose groups were slightly decreased relative to controls in type II skeletal muscle, although the difference was not significantly different in most cases. Mitochondrial function in skeletal muscle was not affected by the changes in ubiquinone levels. The ubiquinone levels in high-dose-treated animals exhibiting myopathy were not significantly different from low-dose animals with no observable toxic effects. Furthermore, ubiquinone levels did not correlate with circulating CK levels in treated animals. The results of this study suggest that neither mitochondrial injury, nor a decrease in muscle ubiquinone levels, is the primary cause of skeletal myopathy in cerivastatin-dosed rats.

Topics: Animals; Drug Evaluation, Preclinical; Female; Mitochondria, Muscle; Muscle, Skeletal; Muscular Diseases; Pyridines; Rats; Rats, Sprague-Dawley; Ubiquinone

Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Product Surveillance, Postmarketing; Pyridines; United States

Topics: Anticholesteremic Agents; Creatine Kinase; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver; Lovastatin; Meta-Analysis as Topic; Muscular Diseases; Pravastatin; Pyridines; Randomized Controlled Trials as Topic; Retrospective Studies; Rhabdomyolysis; Transaminases; Treatment Outcome

Topics: Aged; Colon; Fatal Outcome; Female; Humans; Intestinal Pseudo-Obstruction; Muscular Diseases; Pyridines

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Contraindications; Coronary Disease; Creatine Kinase; Drug Interactions; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Monitoring, Physiologic; Muscular Diseases; Pyridines; Risk Factors

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Contraindications; Coronary Disease; Creatine Kinase; Drug Interactions; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Monitoring, Physiologic; Muscular Diseases; Pyridines; Risk Factors

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Contraindications; Coronary Disease; Creatine Kinase; Drug Interactions; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Monitoring, Physiologic; Muscular Diseases; Pyridines; Risk Factors

Topics: Alanine Transaminase; Animals; Anticholesteremic Agents; Clinical Enzyme Tests; Clinical Trials as Topic; Cohort Studies; Erectile Dysfunction; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Liver; Lovastatin; Male; Muscular Diseases; Peripheral Nervous System Diseases; Pyridines; Risk Assessment; United States; United States Food and Drug Administration

Topics: Anticholesteremic Agents; Drug and Narcotic Control; Humans; Muscular Diseases; Pain; Pyridines

Topics: Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Muscle, Skeletal; Muscular Diseases; Pyridines

Statin induced myopathy is the most commonly seen side effect in users of this family of drugs. Their different forms present with either creatine phosphokinase (CK) elevation or not, signs of in vivo oxidation injury or not or a combination of both. The pathogenetic background, however, still remains obscure. As MIBI, beside myocardial and tumour scintigraphy, is useful in detecting muscle metabolic abnormalities, an increased uptake of MIBI in the diseased muscular segments could be expected. We investigated seven patients (five males, two females; aged 36-56 years) with statin induced myopathy with either elevated CK, isoprostanes or muscle pains at varying combinations. MIBI whole-body imaging was done immediately, the patients still being on the respective statin. Sixteen patients (six males, 10 females) suffering from lung or breast cancer and being on statins served as controls. No uptake abnormalities in any muscular segment either in the patients or the control group were seen. Thus, MIBI scintigraphy is not useful, apparently, in diagnosing and eventually localizing statin induced myopathy. These findings indicate that MIBI scintigraphy is of no help for diagnosis and gaining further insight into statin induced myopathy.

Topics: Adult; Anticholesteremic Agents; Atorvastatin; Breast Neoplasms; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Heterozygote; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Indoles; Lovastatin; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Pain; Pravastatin; Pyridines; Pyrroles; Radionuclide Imaging; Radiopharmaceuticals; Simvastatin; Technetium Tc 99m Sestamibi