BEMNIFOSBUVIR HAS LOW POTENTIAL TO INHIBIT P-gp, BCRP, AND OATP1B1 MEDIATED TRANSPORT

Background: Bemnifosbuvir (BEM, AT-527) is a guanosine nucleotide prodrug candidate for the treatment of COVID-19 and chronic HCV. BEM was identified in vitro as an inhibitor of drug transporters P-glycoprotein, breast cancer resistant protein (BCRP) and organic anion transporting polypeptide 1B1 (OATP1B1). Ph 1 studies in healthy participants were conducted to assess the clinical implications of these results using digoxin (DIG) and rosuvastatin (ROSU) as P-gp and BCRP/ OATP1B1 index drugs, respectively. Method(s): Both studies employed a similar design with 2 groups of 14 healthy participants: Day 1/period 1, all participants received a single dose of DIG 0.25mg or ROSU 10mg alone. In period 2, participants received DIG 0.25mg or ROSU 10mg with BEM 1100mg, simultaneously (n=14) or staggered by 2h (n=14). Serial plasma samples were collected and quantitated for DIG or ROSU concentrations. Result(s): A single dose of BEM 1100mg simultaneously administered slightly increased the Cmax of DIG (78%), yet had no effect on its AUC, consistent with the transient nature of BEM plasma PK. When dosed staggered, BEM did not affect the PK of DIG. A single dose (simultaneous or staggered) of BEM 1100mg slightly increased the plasma exposure of ROSU (20%-40%). There was no effect on vital signs, ECG, and no SAEs or drug discontinuations. Conclusion(s): A single high dose of BEM 1100mg only slightly increased the plasma exposure of the P-gp and BCRP/OATP1B1 index drugs DIG and ROSU. BEM has low potential to exhibit clinical meaningful inhibition of these transporters. No dose adjustment will be needed for drugs that are sensitive substrates of P-gp or BCRP/OAT1B1 when co-administered with BEM, staggered dosing may lessen any DDI risk.

L-Ornithine-L-Aspartate and Intermittent Renal Replacement Therapy in Fulminant Hepatitis A: A Case Report

Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. Since the introduction of an efficient vaccine, the incidence of infection has decreased but the number of cases has risen due to widespread community outbreaks among unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice, and are more common in older children and adults. People are often most infectious 14 days prior to and 7 days following the onset of jaundice. We will discuss the case of a young male patient, diagnosed with acute hepatitis A, leading to fulminant hepatitis refractory to conventional therapy and the development of subsequent kidney injury. The medical treatment through the course of hospitalization was challenging and included the use of L-ornithine-L-aspartate and prolonged intermittent hemodialysis, leading to a remarkable outcome. Hepatitis A is usually self-limited and vaccine-preventable;supportive care is often sufficient for treatment, and chronic infection or chronic liver disease rarely develops. However, fulminant hepatitis, although rare, can be very challenging to manage as in the case of our patient.Copyright © 2023 The Author(s).

Effect Of Rosuvastatin In The Protection Against Azithromycin Induced Cardiotoxicity In Covid-19 Patients: A One-Year Prospective Study

Background Azithromycin is a widely used broad-spectrum antibiotic that was recently used in the treatment protocol of COVID-19 but its cardiac side effects became a more prominent concern. Rosuvastatin is a synthetic statin that showed anti-inflammatory, antioxidant and autonomic nervous system regulatory effects in addition, there is increasing evidence supporting that it could play a beneficial role in patients with COVID-19. Objective To evaluate the protective effect of Rousvastatin against Azithromycin-induced cardiotoxicity in Covid-19 patients. Patients and Methods This is a prospective study that was conducted on adult patients diagnosed with COVID-19 who were admitted to isolation centres in Minia Governorate, Egypt for the period of one year (June 2021 to May 2022). The study included a total of 80 COVID-19 patients who were divided into 2 groups (n=40 each), group (I) "Azithromycin group" that included patients received Azithromycin (500 mg/day for 5 days) orally and group (II) "Azithromycin + Rosuvastatin group" that included patients received Azithromycin by oral route as group (I) plus Rosuvastatin 20 mg/day orally. All included cases were subjected to full history taking, clinical examination and laboratory investigations and after treatment, the outcome measures were reported and compared. Results No significant differences were observed between groups regarding demographic and baseline characteristics. Also, the two groups were comparable with no significant differences in pulse rate, blood sugar, CBC, electrolyte elements, liver enzymes, and kidney function (a slight reduction was noticed in group II). While, Ferritin level was significantly lower in group (II) compared to group (I), (830 ± 72.5 vs. 865 ± 69.5, p=0.03). No significant differences were observed among groups as regards Troponin level (p=0.56) "Only one case was positive in group (I)". Both groups were almost comparable without significant differences in both stages of infection and mortality (p=0.38 and 1.0, respectively). Conclusion Rosuvastatin did not have a significant role in the protection of Azithromycin-induced cardiotoxicity, it slightly ameliorates the biochemical and stress markers alterations of Azithromycin. Further larger studies are warranted for investigating this issue. [ FROM AUTHOR] Copyright of Journal of Pharmaceutical Negative Results is the property of ResearchTrentz and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Alternative Management of Cushing's Syndrome During Covid-19 Pandemic

Cushing's syndrome results from prolonged exposure to glucocorticoids. Surgery is often the first-line treatment for this condition, regardless of etiology. However, the COVID-19 pandemic caused a decrease in surgical procedures due to the risk of infection transmission. There are still emergency cases of Cushing's syndrome that are admitted to the hospital and require urgent management. The current treatment should be focused on medical management and endovascular embolization in selective cases. Embolization can be performed in facilities where there aretrained personnel with experience in adrenal embolization. Surgery, which traditionally is a first-line therapy, can increase the risk of infection, therefore, it should be avoided. The current review provides a brief description of the possible options for the management of adrenal Cushing's syndrome during the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

Effect of Rosuvastatin in the Protection against Azithromycin Induced Cardiotoxicity in Covid-19 Patients: A One-Year Prospective Study

Background Azithromycin is a widely used broad-spectrum antibiotic that was recently used in the treatment protocol of COVID-19 but its cardiac side effects became a more prominent concern. Rosuvastatin is a synthetic statin that showed anti-inflammatory, antioxidant and autonomic nervous system regulatory effects in addition, there is increasing evidence supporting that it could play a beneficial role in patients with COVID-19. Objective To evaluate the protective effect of Rousvastatin against Azithromycin-induced cardiotoxicity in Covid-19 patients. Patients and Methods This is a prospective study that was conducted on adult patients diagnosed with COVID-19 who were admitted to isolation centres in Minia Governorate, Egypt for the period of one year (June 2021 to May 2022). The study included a total of 80 COVID-19 patients who were divided into 2 groups (n=40 each), group (I) "Azithromycin group" that included patients received Azithromycin (500 mg/day for 5 days) orally and group (II) "Azithromycin + Rosuvastatin group" that included patients received Azithromycin by oral route as group (I) plus Rosuvastatin 20 mg/day orally. All included cases were subjected to full history taking, clinical examination and laboratory investigations and after treatment, the outcome measures were reported and compared. Results No significant differences were observed between groups regarding demographic and baseline characteristics. Also, the two groups were comparable with no significant differences in pulse rate, blood sugar, CBC, electrolyte elements, liver enzymes, and kidney function (a slight reduction was noticed in group II). While, Ferritin level was significantly lower in group (II) compared to group (I), (830 +/- 72.5 vs. 865 +/- 69.5, p=0.03). No significant differences were observed among groups as regards Troponin level (p=0.56) "Only one case was positive in group (I)". Both groups were almost comparable without significant differences in both stages of infection and mortality (p=0.38 and 1.0, respectively). Conclusion Rosuvastatin did not have a significant role in the protection of Azithromycin-induced cardiotoxicity, it slightly ameliorates the biochemical and stress markers alterations of Azithromycin. Further larger studies are warranted for investigating this issue. Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

An occurrence of immune-mediated necrotizing myopathy following treatment of polymyositis in a Filipino female: A case report

Background: Necrotizing myopathy has been previously described but was not included in the Peter and Bohan criteria until 2004, when immune-mediated necrotizing myopathy (IMNM) was distinguished from polymyositis (PM) based on immunologic and histopathologic differences. IMNM is currently a well-recognized autoimmune myopathy and represents up to 20% of these cases. Case: A 60-year- old female with biopsy-proven PM achieved sustained clinical remission with Rituximab. Her co-morbid conditions include hypertension, diabetes mellitus, and dyslipidemia. The patient noted a recurrence of gradual progressive, proximal muscle weakness and easy fatigability after receiving her first mRNA Covid-19 vaccine. Four months after onset of symptoms, CK Total was 9600 U/L. Rituximab was administered and muscle weakness and total CK levels (1247 U/L) improved within 10 days. She was prescribed rosuvastatin and fenofibrate for dyslipidemia within 7 days of completing the rituximab course. Two weeks later, proximal muscle weakness recurred. She became wheelchair-bound and experienced dysphonia. MMT score was 2/5 in proximal muscles and total CK total increased to 19,935 U/L. The patient received Methylprednisolone 500 mg IV once a day for 3 days. She had a good response with resolution of dysphonia and improvement of MMT to 4/5 on shoulder abduction and hip flexion on the 6th hospital day. She was discharged on oral methylprednisolone at 1 mg/kg/day. Muscle biopsy was consistent with an immune-mediated necrotizing myopathy, revealing necrotic fibers, intracellular macrophages, fatty infiltrates, irregular staining patterns on NADH stain with no evidence of endomysial inflammation, perifascicular atrophy, ragged red fibers, or rimmed vacuoles. Antibodiy against 3-hydoxy- 3- methylglutarylcoenzymeA reductase (HMGCR) result is pending but the other myositis-specific antibodies are negative.(including anti-SRP). Conclusion(s): IMNM is an autoimmune myopathy associated with anti-HMGCR and anti-SRP antibodies that clinically present similarly to polymyositis. The temporal occurrence of worsening muscle weakness with initiation of statin therapy make statin toxic myopathy or immune mediated necrotizing myopathy as diagnostic considerations. This case emphasizes the need to re-evaluate the etiology of new onset muscle weakness in patients with idiopathic inflammatory myopathy and highlights the role of myositis-specific antibodies and muscle biopsy in confirming the diagnosis.

Therapeutic Options for the Single Pill Combination of Lisinopril, Amlodipine and Rosuvastatin: a Systematic Review

Aim. To evaluate the effect of taking a single pill combination of amlodipine, lisinopril and rosuvastatin on blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in hypertensive patients with or without severe hypercholesterolemia. Material and methods. Articles published in Russian were selected for analysis. Six articles that met the criteria for inclusion in a systematic review were found by searching the eLibrary database for the keyword "equamer". The results of 5 observational clinical studies were presented in these articles. The effectiveness of the fixed combination of amlodipine, lisinopril and rosuvastatin was assessed mainly by changes in the level of systolic and diastolic blood pressure, the concentration of LDL cholesterol. In addition, the effects of fixed-dose amlodipine, lisinopril, and rosuvastatin on central aortic pressure and its increment index, as well as carotid-femoral pulse wave velocity, were studied in part of the studies. The effect of the fixed combination of amlodipine, lisinopril and rosuvastatin on blood pressure and LDL-C concentration, as well as on these additional indicators, in patients who had a coronavirus infection with severe lung damage was studied in one study. Results. Evidence from a systematic review demonstrates the efficacy of single pill combination amlodipine, lisinopril and rosuvastatin in reducing blood pressure and LDL-C in a wide range of patients with different baseline risk of developing cardiovascular complications and different baseline levels of blood pressure and LDL-C. Conclusion. The data obtained confirm the feasibility of more frequent prescription of the single pill combination of amlodipine, lisinopril and rosuvastatin in clinical practice for the treatment of hypertensive patients with high or moderate risk of developing cardiovascular diseases, including patients with concomitant hypercholesterolemia.

Lipid profile of patients with arterial hypertension who underwent COVID-19: possibilities of drug therapy/ LEADER

Aim. To study the dynamics of the lipid profile of hypertensive patients with dyslipidemia who underwent COVID-19. Material and methods. Hypertensive patients with dyslipidemia who underwent COVID-19 [n=126;58 men and 68 women;median age 60 (56.0;65.5) years] examined. Patients were included into two groups: group 1 (n=64) received a single pill combination of lisinopril + amlodipine + rosuvastatin;2 groups (n=62) continued the previous drug treatment. Clinical, demographic, office blood pressure (BP), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol, triglycerides, C-reactive protein (CRP) levels were assessed in all patients in 3 visits within 24 weeks. Results. The groups did not differ in prior antihypertensive therapy (except for more frequent use of angiotensin II receptor blockers in group 2, p<0.05), lipid profile and blood pressure parameters at study entry. A decrease in systolic (by 9.5%) and diastolic blood pressure (by 12.1%) after 24 weeks was found in group 1 compared with 4.29% and 5.56%, respectively, in group 2 (p<0.05). A decrease in the level of total cholesterol by 14.5% and LDL-c by 31.4% after 24 weeks was found in group 1 compared with 11.2% and 9.7%, respectively, in group 2 (p<0.05). The level of CRP during the observation period decreased by 53.7% in group 1 versus 43.4% in patients of group 2 (p<0.05). Conclusion. The single pill combination of lisinopril/amlodipine/rosuvastatin in hypertensive patients with dyslipidemia who underwent COVID-19 led to an improvement in lipid profile and blood pressure control.

OPTIMIZATION OF BLOOD PRESSURE CONTROL AND ANGIOPROTECTION WITH FIXED COMBINATION OF LISINOPRIL + AMLODIPINE + ROSUVASTATIN IN PATIENTS AFTER A COVID-19

Objective: Evaluation of the capability of a fixed combination of lisinopril + amlodipine + rosuvastatin (ECWAMER) in achieving additional angioprotection in patients with arterial hypertension (AH) and high pulse wave velocity (PWV) in patients after confirmed COVID-19 had 75 - 95% lung involvement, complicated by bilateral polysegmental viral pneumonia, with genetically engineered biological drugs (GIBD) therapy, who had not previously received combined antihypertensive therapy (AHT). Design and method: An open-label observational study with a duration of 12 weeks has been carried out. 30 patients who not previously received combined AHT was included. Patients underwent daily monitoring of blood pressure (ABPM), applanation tonometry (determination of the augmentation index (IA) and central blood pressure (CSAD)), measurement of PWV, laboratory tests (lipid composition of blood, fasting glucose, C-reactive protein - CRP, OAC, ferritin, fibrinogen, D-dimer, ALT, AST, creatinine, uric acid) before and after prescribing a fixed combination of lisinopril + amlodipine + rosuvastatin (ECVAMER). Results: At baseline, the patients had an increase in office blood pressure to 152.6 / 89.1 mm Hg. After prescribing a fixed combination of lisinopril + amlodipine + rosuvastatin, there was a decrease in systolic blood pressure (SBP) by 15.8% and diastolic blood pressure (DBP) by 12.2%. According to ABPM data, the decrease in SBP was 15% and DBP - 9%, decreased PWV by 23.8%, IA by 9%, CSAP by 12.4% (p < 0.05 for all comparisons with the baseline value). Vascular age (SV) was initially increased to 41.9 years with a passport age of 35.03 years. After the end of therapy, there was a significant decrease in CO up to 36.5 years, LDL by 46.8%, triglycerides by 16.8% and an increase in HDL by 10.7% (p < 0.05 for all comparisons with the baseline value). In addition, the levels of CRP, fibrinogen, D-dimer, glucose, and uric acid significantly decreased. Conclusions: The fixed combination of lisinopril + amlodipine + rosuvastatin provides better blood pressure control, improved vascular elasticity, and also improves lipid and carbohydrate metabolism in patients, reduces inflammation in patients with hypertension and hyperlipidemia after suffering from severe and extremely severe COVID-19.

Utilization of Remdesivir for COVID-19 in the National Veterans Affairs Healthcare System

Background. As remdesivir (GS-5734) has become a leading treatment for COVID-19, we sought to assess remdesivir utilization patterns, including utilization of concomitant and supportive therapies, and heterogeneity in treatment approaches. Methods. Our retrospective cohort study included hospitalized Veterans with positive COVID-19 PCR tests treated with remdesivir, from 03/2020 through 4/2021. Using exposure mapping of barcode medication administration records and medication dispensings, we assessed other medications received by each patient on each day of remdesivir treatment. Heterogeneity was defined as patterns of treatment (drug & duration) not shared by any other patient. Results. Our study included 13,665 patients with COVID-19 receiving remdesivir. The median time to remdesivir initiation from either positive test or hospital admission was 1 day (interquartile range [IQR] 0-4 and 0-1, respectively). The median duration of remdesivir treatment was 5 days (IQR 4-5 days). Median length of hospital stay was 7 days (IQR 4-13). Inpatient mortality was 13.9% and an additional 6.2% of patients died within 90 days of discharge. The most common concomitant and supportive therapies were anticoagulants/antiplatelets (94.8%;enoxaparin 72.6%, heparin 18.4%, apixaban 10.8%, clopidogrel 6.3%), corticosteroids (90.8%;dexamethasone 87.3%, prednisone 2.9%, methylprednisolone 5.5%), statins (55.8%;atorvastatin 38.2%, simvastatin 7.1%, rosuvastatin 6.0%), antibiotics (41.9%;azithromycin 25.6%, ceftriaxone 13.2%, doxycycline 6.0%, vancomycin 4.9%), angiotensin receptor blockers (11.9%) and angiotensin-converting enzyme inhibitors (20.4%), melatonin (29.7%), and aspirin (35.6%). Concomitant utilization of Janus kinase inhibitors (0.5%), interleukin-6 inhibitors (2.4%), and hydroxychloroquine (0.5%) was low. Heterogeneity in concomitant and supportive therapies during remdesivir treatment was 84.6% (68.3% when assessed as drug class/category). Conclusion. Among hospitalized patients with COVID-19 in the national VA Healthcare system receiving remdesivir, remdesivir was initiated early in the admission and substantial heterogeneity was observed in concomitant and supportive therapies during remdesivir treatment.

Lipid Lowering Effects of Herbal Supplements: A Review

As cardiovascular diseases are still a major cause of death in most countries, it is still relevant to look into treatment of such diseases. Dyslipidemia is one of the important identified risk factors for cardiovascular diseases. As this is largely driven by lifestyle and diet, it may be difficult to control it with lifestyle modifications alone. Currently, Statins remains to be the mainstay therapy for dyslipidemia but this is also met by problems within certain patient population. The drug may be contraindicated in certain patient groups;some patients tend to not respond to Statins;while certain patients may not tolerate the adverse events. This study looked into available literature on studies done on dyslipidemia using plant-based formulations using randomized clinical trial. Based on the review conducted, there are several plant-based formations with potential to be similar in efficacy to Statins. Some of the plants used are abundant or may be easily sourced. With the increasing popularity of food supplements or nutraceuticals, exploration on the potential of plant-based products is attractive. Despite the promising results of some studies, these will need further investigations and targeting a larger population size. Formulation options may need to be explored also focused on its stability. © RJPT All right reserved.

Optimization of blood pressure control, organ protection and metabolic disorders using a fixed-dose combination of lisinopril+amlodipine+rosuvastatin in hypertensive patients after COVID-19

Aim. To evaluate the potential of a fixed-dose combination of lisinopril+amlodi-pine+rosuvastatin (Equamer® ) in achieving additional vascular protection in patients with hypertension and high pulse wave velocity (PWV) after severe and very severe coronavirus disease 2019 (COVID-19), complicated by bilateral multisegmental viral pneumonia, with the use of biological therapy, who had not previously received combination antihypertensive therapy. Material and methods. This 12-week open-label observational study included 30 patients with or without antihypertensive therapy. The patients underwent 24-hour blood pressure monitoring, applanation tonometry (determination of the augmentation index (AI) and central blood pressure (CBP)), PWV measurement, blood laboratory tests (lipid profile, fasting glucose, C-reactive protein, complete blood count, ferritin, fibrinogen, D-dimer, alanine aminotransferase, aspartate aminotransferase, creatinine, uric acid) before and after switch to a fixed-dose combination of lisinopril+amlodipine+rosuvastatin. Results. At baseline, the patients had an increase in office blood pressure (BP) up to 152,6/89,1 mm Hg. After prescribing a fixed-dose combination of lisinopril+amlo dipine+rosuvastatin, there was a decrease in systolic blood pressure (SBP) by 15,8% and diastolic blood pressure (DBP) by 12,2%. According to 24-hour blood pressure monitoring, the decrease in SBP was 15%, DBP — by 9%, PWV — by 23,8%, AI — by 9%, CBP — by 12,4% (p<0,05 for all compared to baseline values). Vascular age (VA) was initially increased to 41,9 years with a chronological age of 35,03 years. After the end of therapy, there was a significant decrease in VA to 36,5 years, low-density lipoproteins by 46,8%, triglycerides by 16,8% and an increase in high-density lipoproteins by 10,7% (p<0,05 for all compared to baseline values). In addition, the levels of C-reactive protein, fibrinogen, D-dimer, glucose, and uric acid significantly decreased. Conclusion. The fixed-dosed combination of lisinopril+amlodipine+rosuvastatin provides better blood pressure control, improved vascular elasticity parameters (AI, PWV, CBP, decrease in VA), and also improves lipid and carbohydrate metabolism, reduces inflammation in patients with hypertension and hyperlipidemia after severe COVID-19.

Central blood pressure lowering effect of telmisartan-rosuvastatin single-pill combination in hypertensive patients combined with dyslipidemia: A pilot study.

This multicenter, phase 4, Prospective Randomized Open, Blinded End-point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single-pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID-19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10-year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4-week single-group run-in period with telmisartan 40-80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial-ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between-group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between-group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between-group difference p = .078). Change of AIx had no significant difference (between-group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.

Protective effect of Rosuvastatin on Azithromycin induced cardiotoxicity in a rat model.

AIMS: Azithromycin is widely used broad spectrum antibiotic recently used in treatment protocol of COVID-19 for its antiviral and immunomodulatory effects combined with Hydroxychloroquine or alone. Rat models showed that Azithromycin produces oxidative stress, inflammation, and apoptosis of myocardial tissue. Rosuvastatin, a synthetic statin, can attenuate myocardial ischemia with antioxidant and antiapoptotic effects. This study aims to evaluate the probable protective effect of Rosuvastatin against Azithromycin induced cardiotoxicity. MAIN METHOD: Twenty adult male albino rats were divided randomly into four groups, five rats each control, Azithromycin, Rosuvastatin, and Azithromycin +Rosuvastatin groups. Azithromycin 30 mg/kg/day and Rosuvastatin 2 mg/kg/day were administrated for two weeks by an intragastric tube. Twenty-four hours after the last dose, rats were anesthetized and the following measures were carried out; Electrocardiogram, Blood samples for Biochemical analysis of lactate dehydrogenase (LDH), and creatine phosphokinase (CPK). The animals sacrificed, hearts excised, apical part processed for H&E, immunohistochemical staining, and examined by light microscope. The remaining parts of the heart were collected for assessment of Malondialdehyde (MDA) and Reduced Glutathione (GSH). KEY FINDINGS: The results revealed that Rosuvastatin significantly ameliorates ECG changes, biochemical, and Oxidative stress markers alterations of Azithromycin. Histological evaluation from Azithromycin group showed marked areas of degeneration, myofibers disorganization, inflammatory infiltrate, and hemorrhage. Immunohistochemical evaluation showed significant increase in both Caspase 3 and Tumor necrosis factor (TNF) immune stain. Rosuvastatin treated group showed restoration of the cardiac muscle fibers in H&E and Immunohistochemical results. SIGNIFICANCE: We concluded that Rosuvastatin significantly ameliorates the toxic changes of Azithromycin on the heart.

Fatal Rhabdomyolysis in a COVID-19 Patient on Rosuvastatin.

It is well-established by now that COVID-19 can have a wide variety of neuromuscular manifestations, including rhabdomyolysis. Weakness and elevated creatinine kinase (CK) have been documented as the initial presentation of COVID-19. Myopathy from statin use has also been well-established since the introduction of this class of medication, and the common pathologic mechanism of both entities may have been mitochondrial dysfunction. We present here the case of a COVID-19 patient on rosuvastatin who developed rhabdomyolysis with CK above 1,000,000 units/L. The patient did not present with any respiratory difficulty and responded poorly to treatment, resulting in his untimely demise. COVID-19 may have accentuated an otherwise survivable condition by means of extra stress on mitochondrial homeostasis. Understanding the actual mechanism will be important in the development and utilization of medications in the fight against COVID-19.