Transfluthrin: comparative efficacy and toxicity of reference and generic versions.

Stringent requirements are in place for the evaluation and registration of new compounds with biocidal or pesticidal activities. However, the registration requirements for established compounds from new suppliers or for established compounds produced by a different manufacturing process have been less clear and ambiguity exists as to how 'equivalence of health hazards' can unequivocally be demonstrated analytically and by toxicological assays. The case presented in this analysis focuses on the chiral pyrethroid transfluthrin (TFL) synthesized by esterification of an acid chloride and alcoholic moiety. According to any modifications of the process of synthesis and purification, new potentially highly toxic and yet chemically reactive impurities in low concentrations (<0.1%) may be formed. Amongst these, that with the structural alert 'organic acid anhydride' was given heightened concern as the most potent putative toxicologically significant impurity. The course taken in this analysis focused on the comparison of reference TFL with commercialized generic TFL from two alternative manufacturing sources in India and China. Despite their apparent high racemic purity, TFLs from generic sources were biologically less effective, genotoxic in the Ames' assay, demonstrated sensory lung irritation and lung/skin sensitization in specialized bioassays. While the off-patent reference TFL was unequivocally negative in all assays (anhydride content not detectable, LOQ <0.01%), positive results with high batch-to-batch variability were a frequent outcome in generic TFLs. Tier I analytical assays failed to detect this relevant impurity in the absence of impurity-specific optimized analytical procedures. This finding suggests that a well-balanced combined approach of analytical and toxicological assays provides the best means to assure that all critical impurities are identified and accounted for. Similarly, putative 'structural alert'-based toxicity tests proved to be more predictive than any indiscriminant battery of standard bioassays commonly applied to demonstrate equivalence, such as acute oral/dermal toxicity and/or eye/skin irritation assays.

Genotoxicity evaluation of HMG CoA reductase inhibitor rosuvastatin.

The genotoxic potential of rosuvastatin as one of the statin drugs was assessed by chromosomal aberrations (CAs), micronucleus (MN) and DNA damage by comet assay in the human peripheral blood lymphocytes. Rosuvastatin was used at concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 µg/mL for these in vitro assays. In all assays, a negative and positive control were also included. CA frequencies were significantly increased in all concentrations at 24 hours and significantly increased in all concentrations except 0.0625 µg/mL at 48 hours, compared to the negative control. Rosuvastatin has a decreased mitotic index (MI) at 0.5- and 1-µg/mL concentrations at 24 hours and at 0.25, 0.5 and 1 µg/mL at 48 hours. A significant increase was observed for induction of MN in all treatments, compared to the negative control. Cytokinesis-block proliferation indices were not affected by treatments with rosuvastatin. In the comet assay, significant increases in comet tail length and tail moment were observed at 0.0625-, 0.5- and 1-µg/mL concentrations. Comet intensity was significantly increased in all concentrations except 0.0625 µg/mL. According to these results, rosuvastatin is cytotoxic and clastogenic/aneugenic in human peripheral lymphocytes. Further studies should be conducted in other test systems to evaluate the full genotoxic potential of rosuvastatin.

LC-MS/TOF, LC-MSn, on-line H/D exchange and LC-NMR studies on rosuvastatin degradation and in silico determination of toxicity of its degradation products: a comprehensive approach during drug development.

The present study dealt with the forced degradation behaviour of rosuvastatin under ICH prescribed stress conditions. The drug was found to be labile under acid hydrolytic and photolytic conditions, while it was stable to base/neutral hydrolytic, oxidative and thermal stress. In total, 11 degradation products were formed, which were separated on a C-18 column using a stability-indicating method. LC-MS analyses indicated that five degradation products had the same molecular mass as that of the drug, while the remaining six had 18 Da less than the drug. Structure elucidation of all the degradation products was executed using sophisticated and modern structural characterization tools, viz. LC-MS/TOF, LC-MS(n), on-line H/D exchange and LC-NMR. The degradation pathway and mechanisms of degradation of the drug were delineated. Additionally, in silico toxicity was predicted for all the degradation products using TOPKAT and DEREK software and compared with the drug. This study demonstrates a comprehensive approach of degradation studies during the drug development phase.

Toxicological effects of prolonged and intense use of mosquito coil emission in rats and its implications on malaria control.

Mosquito coil is a vector control option used to prevent malaria in low income counties, while some studies have addressed this issue, additional reseach is required to increase knowledge on the adverse health effects caused by the prolonged use of coils. In this study we investigated the toxicological effects of fumes from two locally manufactured mosquito coil insecticides (with pyrethroids: transfluthrin and d-allethrin as active ingredients) on male albino rats. For this, we recorded the haematological and biochemical indices, and made histopathology and mutagenicity evaluations in rats exposed to mosquito fumes during 2, 4, 8, 12 and 16 week periods. Haematological determination was performed using automated hematology analyzer to determine White Blood Cell (WBC), Packed Cell Volume (PCV), Red Blood Cell (RBC) and Platelet (PLT) counts, while biochemical evaluations were determined using available commercial kits. Gross histopathological changes were studied for the kidney, liver and lungs in sacrificed rats. The rat sperm head abnormalities assessment was used to evaluate mutagenicity. Mosquito coil fumes produced significant increase (P < 0.05) in the levels of total protein, total albumin and bilirubin, when animals were exposed from two weeks to 16 weeks with transfluthrin. Similarly, elevation in the activities of aspartate amino transferase, alanine amino transferase and alanine phosphatase, increased significantly in both insecticides. Increase in WBC, RBC and PCV were recorded for all the exposure periods, however PLT count showed no significant increase (P > 0.05). Mutagenicity assessment revealed sperm abnormality was statistically significant (P < 0.05) compared with the control at 8, 12 and 16 weeks post exposure to transfluthrin. Histological studies revealed severe lung damage evidenced by interstitial accumulations, pulmonary oedema and emphysema in exposed rats. Intracellular accumulations and severe sinusoidal congestion of liver cells were observed from 12 weeks exposure, indicating liver damage. Our studies indicate that mosquito coil fumes do initiate gradual damage to the host. These pathological effects must be taken into consideration by the malaria control program, particularly when regulating their long term and indoor usage.

Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABA(A) [corrected] receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function.

The aim of the present paper was to study the effects of GABAA receptor-positive modulators (L-838417 and NS11394) showing a preference for α2/3 subunits of the GABAA receptor, in models of pain, anxiety, learning, memory and motor function. These compounds have been suggested to have a favourable therapeutic profile over nonselective compounds such as diazepam. In this study, we tested both compounds for their effects in rat models of formalin-induced pain, spinal nerve-ligation-induced mechanical allodynia, plus maze, open field, rotarod, balance beam walking, contextual fear conditioning and Morris water maze. Both compounds exerted analgesic, but no anxiolytic effects. However, they induced motor side-effects, and learning and memory impairment at similar doses. Therefore, the anxiolytic effect and the lack of side-effects of these compounds, as described in the literature, could not be confirmed in the present study.

Effect of mosquito mats (pyrethroid-based) vapor inhalation on rat brain cytochrome P450s.

The effect of transfluthrin (TF) or D-allethrin (DA) pyrethroid (PYR) vapors, often contained as main ingredients in two commercially available mosquito repellent mats, on cytochrome P450 (CYP) enzymes of rat brain and liver was assessed. Immunodetection of CYP2E1 and CYP3A2 proteins revealed their induction in cerebrum and cerebellum, but not in liver microsomes of rats exposed by inhalation to TF or DA. This overexpression of proteins correlated with an increase of their catalytic activities. The specifically increased expression of CYP isoenzymes, due to PYR exposure in the rat brain, could perturb the normal metabolism of endogenous and xenobiotic compounds and leads to increased risks of neurotoxicity by bioactivation, lipid peroxidation and DNA damage.

Renal toxicity of lisinopril and rosuvastatin, alone and in combination, in Wistar rats.

The aim of study was to evaluate the effect of commonly used lisinopril, rosuvastatin and their combined action on site-specific nephrotoxicity in rats using clusterin and microalbumin nephrotoxic biomarkers and other related parameters using oral gavage. Rosuvastatin at 2 different doses showed increase in urinary microalbumin levels whereas lisinopril and its combination with rosuvastatin at 2 different doses did not show urinary microalbumin excretion indicating beneficial effects of lisinopril in terms of reducing microalbumin. Urinary clusterin levels significantly increased in high-dose treated animals of lisinopril and rosuvastatin. The use of lisinopril plus rosuvastatin at low dose also led to worsened renal function by raising urinary clusterin levels (217 ± 4.6 ng/ml) when compared with the control (143 ± 3.3 ng/ml). Renal histopathology showed multifocal regeneration of tubules indicating proximal tubule damaged. These results indicate that lisinopril (50 mg/kg), rosuvastatin (100 mg/kg), lisinopril+rosuvastatin (20+40 mg/kg) and lisinopril+rosuvastatin (50+100 mg/kg) showed toxicity only on proximal tubules.

Toxicity Assessment of Transfluthrin, Benzyl Butyl Phthalate, and 17ß-Estradiol on the Primary Fibroblast of the Striped Field Mouse, Apodemus agrarius.

Environmental pollution (EP) is a well-known threat to wild animals, but its toxicological impact is poorly understood. In vitro toxicity evaluation using cells of lower predators could be a promising way to assess and monitor the effects of EPs on whole wildlife populations that are related in the food web. Here, we describe EPs' toxic effect and mechanism in the primary fibroblast derived from the embryo of the striped field mouse, Apodemus agrarius. Characterization of the primary fibroblast was via morphology, genetics, immunocytochemistry, and stable culture conditions for optimal toxicity screening. Cell viability assays-MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH)-were performed to observe cytotoxicity, and quantitative PCR was conducted to confirm gene alteration by EP exposure. MTT and LDH assays confirmed the cytotoxicity of transfluthrin (TF), benzyl butyl phthalate (BBP), and 17ß-estradiol (E2) with IC50 values of 10.56 µM, 10.82 µM, and 24.08 µM, respectively, following 48-h exposures. mRNA expression of androgen-binding protein, growth hormone receptor, cytochrome C oxidase, and cytochrome P450-1A1 was induced after exposure to TF, BBP, and E2. We unveiled new EP mechanisms at the mammalian cellular level and discovered potential biomarker genes for monitoring of EPs. Based on our findings, we propose the primary fibroblast of A. agrarius as a valuable model to assess the toxicological effects of EP on wildlife.

Rosuvastatin promotes osteoblast differentiation and regulates SLCO1A1 transporter gene expression in MC3T3-E1 cells.

Rosuvastatin (RSV) is a synthetic statin with favourable pharmacologic properties including minimal metabolism, hepatic selectivity and enhanced inhibition of HMG-CoA reductase. An induction of osteoblast differentiation has been reported in vitro with lipophilic statins but not with RSV, which, like pravastatin, is relatively hydrophilic compared with other statins. To mediate its action, an active transport mechanism via solute carrier (SLC) transporters from the SLC16, SLC21/SLCO and SLC22 gene family - specifically Slc16a1, Slco1a1, Slco2b1 and Slc22a8 - may be present to allow effective entry in osteoblastic cells. In this study, we demonstrate that RSV induced osteoblast differentiation, as measured by increased BMP-2 gene expression and secretion, and ALP activity in MC3T3-E1 osteoblast cells, without significantly affecting cell proliferation within the concentration range of 0.001-10 µM. Low concentrations of RSV (0.001-0.01 µM) were protective against cell death whereas higher concentrations (10-100 µM) showed cytotoxicity. Moreover, MC3T3-E1 osteoblasts expressed high levels of Slco1a1 and Slc16a1 mRNA and low levels of Slco2b1 and Slc22a8 mRNA, when compared with kidney and liver tissues from mice. Slco1a1 gene expression increased 12-fold during osteoblast differentiation and was further regulated after RSV treatment. In conclusion, as for other statins, RSV promotes osteoblast differentiation, and also, demonstrated for the first time, regulates the expression of Slco1a1, which may constitute the transport system for RSV across the cell membrane in mature osteoblasts.

Antioxidant, antinociceptive and anti-inflammatory activities of atorvastatin and rosuvastatin in various experimental models.

The present study was planned to investigate the antioxidant, antinociceptive, and anti-inflammatory activities of atorvastatin and rosuvastatin (1, 3 and 10 mg/kg, p.o.) in various animal models. The antinociceptive effect was assessed by chemically- (formalin, acetic acid) and thermally- (hot plate) induced nociception, while anti-inflammatory effect was evaluated using carrageenan-, formaldehyde-induced paw oedema and cotton pellet-induced granuloma. The effect of atorvastatin and rosuvastatin on liver antioxidant enzymes like superoxide dismutase, glutathione, LPO, CAT along with the effect on lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) was evaluated in the cotton pellet-induced granuloma model. Atorvastatin and rosuvastatin showed significant decrease (p < 0.05) in carrageenan- and formaldehyde-induced rat paw oedema and reduced granuloma formation in the cotton pellet-induced granuloma method (p < 0.01) while the levels of LDH and ALP were also significantly decreased (p < 0.05). The liver antioxidant enzyme levels were found to be restored (p < 0.05). Atorvastatin and rosuvastatin also showed antinociceptive activities (p < 0.05 and p < 0.01) in the acetic acid- and formalin-induced nociception in mice, while there was no significant activity in the hot plate method. The present findings suggest that atorvastatin and rosuvastatin possess dose-dependent antioxidant, analgesic, and anti-inflammatory activities.

Comparison of the effects of the synthetic pyrethroid Metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes.

High doses of Metofluthrin (MTF) have been shown to produce liver tumours in rats by a mode of action (MOA) involving activation of the constitutive androstane receptor leading to liver hypertrophy, induction of cytochrome P450 (CYP) forms and increased cell proliferation. The aim of this study was to compare the effects of MTF with those of the known rodent liver tumour promoter phenobarbital (PB) on the induction CYP2B forms and replicative DNA synthesis in cultured rat and human hepatocytes. Treatment with 50 microM MTF and 50 microM PB for 72 h increased CYP2B1 mRNA levels in male Wistar rat hepatocytes and CYP2B6 mRNA levels in human hepatocytes. Replicative DNA synthesis was determined by incorporation of 5-bromo-2'-deoxyuridine over the last 24 h of a 48 h treatment period. Treatment with 10-1000 microM MTF and 100-500 microM PB resulted in significant increases in replicative DNA synthesis in rat hepatocytes. While replicative DNA synthesis was increased in human hepatocytes treated with 5-50 ng/ml epidermal growth factor or 5-100 ng/ml hepatocyte growth factor, treatment with MTF and PB had no effect. These results demonstrate that while both MTF and PB induce CYP2B forms in both species, MTF and PB only induced replicative DNA synthesis in rat and not in human hepatocytes. These results provide further evidence that the MOA for MTF-induced rat liver tumour formation is similar to that of PB and some other non-genotoxic CYP2B form inducers and that the key event of increased cell proliferation would not occur in human liver.

Statin-induced myopathy in the rat: relationship between systemic exposure, muscle exposure and myopathy.

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.

Gone in 60 seconds: Sub-lethal Effects of Metofluthrin Vapors on Behavior and Fitness of Resistant and Field Strains of Aedes aegypti (Diptera: Culicidae).

Spatial repellents can reduce fecundity and interrupt oviposition behavior in Aedes aegypti. Yet, it is unclear if short exposure times, resistant phenotypes, and other aspects of spatial repellents can impact these effects on mosquito reproduction. To address these issues, pyrethroid susceptible, pyrethroid resistant, and field strains of Ae. aegypti were used to evaluate the extent to which fecundity and oviposition behavior are affected following metofluthrin exposure. Mosquitoes were exposed for 60 s to a sub-lethal dose (LC30) of metofluthrin before blood feeding and allowed 72 h to become gravid before evaluation in an oviposition bioassay for an additional 72 h. Metofluthrin-exposed susceptible, field, and to a lesser extent resistant strain Ae. aegypti showed oviposition across fewer containers, less egg yield, less egg viability, and reduced larval survivorship in hatched eggs compared to unexposed cohorts. Susceptible mosquitoes retained some eggs at dissection following bioassays, and in one case, melanized eggs retained in the female. Treated resistant and field strain F1 larvae hatched significantly earlier than unexposed cohorts and resulted in increased larval mortality in the first 3 d after oviposition. Upon laying, the treated field strain had incompletely melanized eggs mixed in with viable eggs. The treated field strain also had the lowest survivorship of larvae reared from bioassay eggs. These results indicate that metofluthrin could succeed in reducing mosquito populations via multiple mechanisms besides acute lethality. With the available safety data, pre-existing spatial repellent registration, and possibilities for other outdoor delivery methods, metofluthrin is a strong candidate for transition into broader mosquito abatement operations.

Role of multi-drug resistance-associated protein-1 transporter in statin-induced myopathy.

This study investigated the effects of probenecid to inhibit the multi-drug resistance-associated protein-1 (MRP-1) in mediating the efflux and myotoxicity in rat skeletal muscles, with administration of rosuvastatin. Male Sprague-Dawley rats were administered daily, for 15 days, with either rosuvastatin (50, 100 or 200 mg/kg) or probenecid (100 mg/kg) alone, or with a combination of rosuvastatin (50, 100 or 200 mg/kg) and probenecid (100 mg/kg). Skeletal muscle toxicity was elevated with probenecid administered with 200 mg/kg/day of rosuvastatin, with the elevation of creatine kinase by 12-fold, alanine aminotrasferase by 10-fold and creatinine by 9-fold at day 15, with no adverse effects observed when probenecid was given alone. Mitochondria ultrastructural damage with enlargement, disruption, cristolysis and vaculation was seen in the soleus and plantaris of animals administered with probenecid and high dosages of statin. These muscles were also expressing more succinic dehydrogenase (SDH)-positive and cytochrome oxidase (CyOX)-positive fibers. Although generally well-tolerated, statins produce a variety of adverse skeletal muscle events. Hydrophilic statins, with reduced levels of non-specific passive diffusion rates into extra-hepatic tissues, are still seen to produce myopathy. This highlights the important roles of transport mechanisms in statin transport at the skeletal muscles. Excessive influx, reduced efflux or the combination of the two could result in elevated cellular levels of statins at the skeletal muscles, resulting in toxicity. This study provides preliminary evidence that the MRP-1 transporter and efflux at skeletal muscles possibly play significant roles in statin-induced myopathy.

Rosuvastatin: characterization of induced myopathy in the rat.

Rosuvastatin is a relatively new member of the statin family (HMG-CoA reductase inhibitors), with superior lipid-lowering effects and a pattern of clinical side effects, including a low incidence of myopathy, similar to other widely prescribed statins. This article describes investigations of myopathy in the rat following administration of very high doses of rosuvastatin. The nature of the changes were found to be entirely consistent with those seen with other statins, including a differential sensitivity of muscle fibers (with glycolytic fibers [type IIB] the most sensitive and oxidative fibers [type I] the least), a delay of approximately 10 days after the start of oral dosing before necrosis was apparent, and ultrastructural alterations appearing first in mitochondria. In addition, the development of myopathy was prevented by coadministration of mevalonate, the product of HMG-CoA reductase. The findings illustrate a pattern of induced myopathy in the rat directly attributable to inhibition of HMG-CoA reductase that is entirely consistent between the various statins, with the oral dose required to produce the changes being a differentiating feature (based on these new data and a previously reported study from the same laboratory): cerivastatin dose less than simvastatin, and simvastatin dose less than rosuvastatin.

Effect of medium pH on the cytotoxicity of hydrophilic statins.

PURPOSE: The aim of this study was to examine the mechanism of pravastatin- and rosuvastatin-induced cytotoxicity and the relationship between pravastatin- and rosuvastatin-induced cytotoxicity and medium pH using human prototypic embryonal rhabdomyosarcoma cell line (RD) and rat myoblast cell line (L6) as a model of in vitro skeletal muscle. METHODS: Statin-induced reduction of cell viability and apoptosis was measured by 3-(4,5-dimethylthiazol-2-yl)2,5 -diphenyl tetrazolium bromide (MTT) assay and caspase assay. Intracellular accumulation of statins was determined using an HPLC system. RESULTS: Rosuvastatin cytotoxicity, reduction of cell viability, morphological changes and caspase activation at acidic pH (pH 6.8) were significantly greater than those at neutral pH (pH 7.4). Rosuvastatin accumulation at acidic pH was greater than that at pH 7.4. On the other hand, medium pH had no effect on pravastatin accumulation. CONCLUSIONS: Rosuvastatin cytotoxicity at acidic pH is associated with increasing intracellular accumulation of rosuvastatin. On the other hand, medium pH had no effect on cytotoxicity of pravastatin.

Preventive effects of bicarbonate on cerivastatin-induced apoptosis.

Although HMG-CoA reductase inhibitors such as statins are the most widely used cholesterol-lowering agents, there is a risk of myopathy or rhabdmyolysis occurring in patients taking these drugs. It has been reported that a number of lipophilic statins cause apoptosis in various cells, but it is still not clear whether intracellular acidification is involved in statin-induced apoptosis. There have been few studies aimed at identifying compounds that suppress statin-induced myotoxicity. In the present study, we examined the relationship between cerivastatin-induced apoptosis and intracellular acidification and the effect of bicarbonate on cerivastatin-induced apoptosis using an RD cell line as a model of in vitro skeletal muscle. Cerivastatin reduced the number of viable cells and caused dramatic morphological changes and DNA fragmentation in a concentration-dependent manner. Moreover, cerivastatin-induced apoptosis was associated with intracellular acidification and caspase-9 and -3/7 activation. On the other hand, bicarbonate suppressed cerivastatin-induced pH alteration, caspase activation, morphological change and reduction of cell viability. Accordingly, bicarbonate suppressed statin-induced apoptosis. The strategy to combine statins with bicarbonate can lead to reduction in the chance of the severe adverse events including myopathy or rhabdmyolysis.

Field evaluation of spatial repellency of metofluthrin-impregnated latticework plastic strips against Aedes aegypti (L.) and analysis of environmental factors affecting its efficacy in My Tho City, Tien Giang, Vietnam.

Spatial repellency of metofluthrin-impregnated polyethylene latticework plastic strips against Aedes aegypti mosquitoes was evaluated. Analysis of environmental factors affecting the efficacy of these strips, such as room temperature, humidity, and house structure, was performed in a residential area in My Tho City, Tien Giang Province, Vietnam. Treatment with the strips at the rate of 1 strip per 2.6-5.52 m(2) (approximately 600 mg per 2.6-5.52 m(2)) reduced the collection of Ae. aegypti resting inside the houses for at least eight weeks. Multiple regression analysis indicated that both increase in the average room temperature and decrease in the area of openings in the rooms that were treated with the strips positively affected the spatial repellency of metofluthrin.

Efficacy and safety of rosuvastatin in treatment of dyslipidemia.

PURPOSE: The chemistry, pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, dosage and administration, and place in therapy of rosuvastatin are reviewed. SUMMARY: Rosuvastatin, the latest statin to receive approved labeling by the Food and Drug Administration, has shown superior efficacy in lowering low-density-lipoprotein (LDL) cholesterol. At daily doses of 5-40 mg, rosuvastatin produces mean reductions in plasma LDL cholesterol of 45-63%, statistically greater than those achieved with equivalent doses of atorvastatin, simvastatin, and pravastatin. Rosuvastatin also improves triglyceride, non-high-density lipoprotein (HDL)-cholesterol, and HDL cholesterol levels to produce a more favorable lipid profile. Rosuvastatin's safety was studied in more than 10,000 patients, exceeding the number of patients evaluated before the launch of any other statin. Many of these patients took the drug for up to 96 weeks. With regard to muscle, renal, and hepatic toxicity and the withdrawal rate due to adverse events, rosuvastatin demonstrates a safety profile similar to that of the other marketed statins. Rosuvastatin undergoes only minor metabolism (10% of the administered dose) by the cytochrome P-450 2C9 isoenzyme. Significant drug interactions were reported with cyclosporine, gemfibrozil, warfarin, and antacids. Evidence suggests that rosuvastatin will be a valuable addition to the choices for treatment of patients with dyslipidemia. CONCLUSION: Rosuvastatin has greater efficacy in lowering LDL cholesterol and non-HDL-cholesterol concentrations than the other statins. It has been shown to enable more patients to reach their LDL cholesterol goals than other statins and to do so with an acceptable safety profile.

Photocatalytic degradation of rosuvastatin: analytical studies and toxicity evaluations.

Photocatalytic degradation of rosuvastatin, which is a drug that has been used to reduce blood cholesterol levels, was studied in this work employing ZnO as catalyst. The experiments were carried out in a temperature-controlled batch reactor that was irradiated with UV light. Preliminary the effects of the photocatalyst loading, the initial pH and the initial rosuvastatin concentration were evaluated. The experimental results showed that rosuvastatin degradation is primarily a photocatalytic process, with pseudo-first order kinetics. The byproducts that were generated during the oxidative process were identified using nano-ultra performance liquid chromatography tandem mass spectrometry (nano-UPLC-MS/MS) and acute toxicity tests using Daphnia magna were done to evaluate the toxicity of the untreated rosuvastatin solution and the reactor effluent.