No abstract available.
Humans ; Hypercholesterolemia* ; Lovastatin*

No abstract available
Fluorouracil* ; Lovastatin* ; Stomach Neoplasms* ; Stomach* ; Thymidylate Synthase

No abstract available.
Animals ; Glomerulosclerosis, Focal Segmental* ; Lovastatin* ; Puromycin* ; Rats*

BACKGROUND: This study was designed to evaluate the clinical efficasy of lovastatin, HMG-CoA reductase inhibitor, in patients with hypercholesterolemia. METHODS AND RESULTS: Lovastatin 20 to 80 mg were administered once daily for 12 weeks in twenty five patients(11 male, 14 famale ; nine patients with familial hypercholesterolemia) with hypercholesterolemia(>240mg/dl). Compared with pretreatment levels, lovastatin significantly decreased levels of total cholesterol(309+/-46mg/dl versus 201+/-37mg/dl) by 35%, LDL-cholesterol(230+/-48mg/dl versus 125+/-40mg/dl) by 46% and triglyceride(170+/-76 versus 142+/-66mg/dl) by 11% (p<0.05) with significantly decreased levels of total-cholesterol/HDL-cholesterol ratio(7.4+/-2.1 versue 4.6+/-1.5) and LDL-cholesterol/HDL-cholesterol ratio(5.6+/-1.9 versue 2.9+/-1.4) (p<0.005 except triglyceride, respectively). The level of Apo B(183+/-32mg/dl versus 114+/-26mg/dl) was decreased significantly by 37%(p<0.005) with significantly decreased level of Apo A-1(115+/-22 to 122+/-26mg/dl) was increased significantly by 6%(p<0.05). No serious side effects were found. CONCLUSIONS: Results from the present study show that lovastatin is an effective and well-tolerated cholesterol-lowering agent.
Humans ; Hypercholesterolemia* ; Lovastatin* ; Male ; Oxidoreductases ; Triglycerides

Adrenoleukodystrophy ; genetics ; therapy ; Humans ; Lovastatin ; pharmacology

Simvastatin is a lipid-lowering drug that is metabolized to its active metabolite simvastatin acid (SA). We developed and validated a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to quantitate SA in human plasma using a liquid-liquid extraction method with methanol. The protonated analytes generated in negative ion mode were monitored by multiple reaction monitoring. Using 500-mL plasma aliquots, SA was quantified in the range of 0.1-100 ng/mL. Calibration was performed by internal standardization with lovastatin acid, and regression curves were generated using a weighting factor of 1/χ2. The linearity, precision, and accuracy of this assay for each compound were validated using quality control samples consisting of mixtures of SA (0.1, 0.5, 5, and 50 ng/mL) and plasma. The intra-batch accuracy was 95.3-107.8%, precision was -2.2% to -3.7%, and linearity (r2) was over 0.998 in the standard calibration range. The chromatographic running time was 3.0 min. This method sensitively and reliably measured SA concentrations in human plasma and was successfully used in clinical pharmacokinetic studies of simvastatin in healthy Korean adult male volunteers.
Adult ; Calibration ; Humans* ; Liquid-Liquid Extraction ; Lovastatin ; Male ; Mass Spectrometry* ; Methanol ; Plasma* ; Protons ; Quality Control ; Running ; Simvastatin* ; Volunteers

Statin-induced rhabdomyolysis is a frequent complication in renal transplant recipients receiving cyclosporine, but incidences are different between different types of statins. Statins have different pharmacokinetic properties. Atorvsatatin, simvastatin, lovastatin, and cerivastatin are all metabolized by the cytochrome P450 isoenzyme 3A4 and co-administration of cyclosporine which may inhibit cytochrome P450 isoenzyme 3A4, increases statin levels and therefore increases the risk of rhabdomyolysis. Fluvastatin is metabolized by cytochrome P450 isoenzyme 2C9 and no clinically significant interactions with cyclosporine have been reported. Atorvastatin with co-administration of cyclosporine in renal transplant patients may induce drug interactions, therefore we recommend the routine monitoring of muscle enzymes, in these cases. Here, we reported a case of rhabdomyolysis in a patient who received atorvastatin and cyclosporine with the review of the literature.
Cyclosporine ; Cytochrome P-450 Enzyme System ; Drug Interactions ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Lovastatin ; Rhabdomyolysis* ; Simvastatin ; Transplantation* ; Atorvastatin Calcium

OBJECTIVE: The aim of this study is to compare cholesterol lowering effects of low dose 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in Korean patients. METHODS: A total of 909 consecutive patients were enrolled prospectively according to the criteria of National Cholesterol Education Program guidelines. Lipid profiles were obtained before and 2 months after statin therapy. RESULTS: Atorvastatin 10 mg (n=260), lovastatin 20 mg (n=145), pitavastatin 2 mg (n=80), pravastatin 20 mg (n=28), rosuvastatin 5 mg (n=145), and simvastatin 20 mg (n=208) reduced low density lipoprotein (LDL) cholesterol by -41.8+/-11.0%, -33.8+/-12.8%, -39.3+/-10.8%, -31.5+/-8.9%, -48.8+/-12.3%, and -42.8+/-13.5%, respectively. LDL cholesterol less than 130 mg/dL was achieved in 90.3%, 76.9%, 88.5%, 85.2%, 97.2%, and 94.2%, respectively. The reduction of LDL cholesterol by 30% or more was obtained in 84.4%, 60.7%, 81.6%, 63.0%, 93.0%, and 83.5%, respectively. LDL cholesterol less than 70 mg/dL or the reduction by 50% or more was observed in a small portion of patients and was variable according to the different types of statins. CONCLUSION: A low dose statin was enough to manage dyslipidemia in most Korean patients with low to moderate risks and was even effective in a subpopulation of high risk patients.
Cholesterol* ; Cholesterol, LDL ; Coenzyme A ; Dyslipidemias ; Education ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Hypercholesterolemia ; Lipoproteins ; Lovastatin ; Oxidoreductases ; Pravastatin ; Prospective Studies ; Simvastatin ; Atorvastatin Calcium ; Rosuvastatin Calcium

Simvastatin, a semisynthetic derivertive of lovastatin, is an important drug for the treatment of hypercholesteromia, and is traditionally prepared by direct alkylation of lovastatin. Chemical reaction conditons are very rigid, and the final product is difficult to purify, also the pressure of labor protection and environment protection is very high. Recently, with the devolpement in the research of lovastatin biosynthesis, more and more attention has been paid to simvastatin biosynthesis. This paper compared the chemical and biological routes in simvastatin production. Simvastatin could be produced by direct fermentation with combinational biosynthesis method, and could also be synthesized from monacolin J with acyltransferase LovD.
Acyltransferases ; genetics ; metabolism ; Anticholesteremic Agents ; metabolism ; Catalysis ; Escherichia coli ; genetics ; metabolism ; Fermentation ; Lovastatin ; analogs & derivatives ; biosynthesis ; Naphthalenes ; metabolism ; Simvastatin ; metabolism ; Transformation, Bacterial

BACKGROUND: The HMG-CoA reductase inhibitor is the most powerful cholesterol lowering drug and lovastatin, simvastatin and pravastatin are used clinically. We studied the efficacy and side effects of pravastatin monotherapy in patients with hypercholesterolemia(type IIa or IIb). METHODS: Patients who showed 12-hours fasting serum total cholesterol level more than 240mg% were enrolled to diet therapy. After 4weeks of diet therapy, serum lipid profiles were checked and the drug therapy was considered according to NCEP guidelines. The pravastatin 5mg po bid was administrated and the patients had regular follow-up every 2weeks for 8week. RESULTS: The total study population was 20 patients and the mean age of them was 55 years old (55+/-18, M : F=6 : 14). There were a few side effects in 5% of study patients and no patient discontinued pravastatin due to side effects.The side effect was G-I trouble and there were not other side effects. Serum CK was elevated in only one patient but the elevation was mild(less than 3 times) and transient. The LFT, serum uric acid, BUN and creatinine level did not show any significant changes during therapy. Among lipid profiles, total cholesterol, LDL-cholesterol and apolipoprotein B level showed significant reduction after therapy and the maximum reduction was achieved after 2week of therapy. The mean reduction was 20%, 33% and 23% respectively. HDL-cholesterol and apolipoprotein A1 11% and 17% respectively. The triglyceride level did not show any changes during therapy but in one type IIb patient, the triglyceride level decreased significantly. CONCLUSIONS: The pravastatin is effective and safe in patients with hypercholesterolemia.
Apolipoprotein A-I ; Apolipoproteins ; Cholesterol ; Creatinine ; Diet Therapy ; Drug Therapy ; Fasting ; Follow-Up Studies ; Humans ; Hypercholesterolemia* ; Lovastatin ; Middle Aged ; Oxidoreductases ; Pravastatin* ; Simvastatin ; Triglycerides ; Uric Acid