HMG‐CoA Reductase Inhibitors: An Exciting Development in the Treatment of Hyperlipoproteinemia

Kathawala, F. G.

doi:10.1002/j.1098-1128.1991.tb00001.x

Cited by 104 publications

(13 citation statements)

References 25 publications

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“…The site of action of statins is within the hepatocytes, and fluvastatin efficacy is therefore related to the hepatocyte exposure to 3R,5S‐fluvastatin . The maximum fluvastatin dose (80 mg/day) reduces Low‐density lipoprotein cholesterol on average by 33%, which is less than that seen with the maximum doses of rosuvastatin and atorvastatin.…”

Section: Discussionmentioning

confidence: 99%

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Enantiospecific Pharmacogenomics of Fluvastatin

Hirvensalo

Tornio

Neuvonen

et al. 2019

Clin Pharma and Therapeutics

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The aim of this study was to investigate how variability in multiple genes related to pharmacokinetics affects fluvastatin exposure. We determined fluvastatin enantiomer pharmacokinetics and sequenced 379 pharmacokinetic genes in 200 healthy volunteers. CYP2C9*3 associated with significantly increased area under the plasma concentration‐time curve (AUC) of both 3R,5S‐fluvastatin and 3S,5R‐fluvastatin (by 67% and 94% per variant allele copy, P = 3.77 × 10−9 and P = 3.19 × 10−12). In contrast, SLCO1B1 c.521T>C associated with increased AUC of active 3R,5S‐fluvastatin only (by 34% per variant allele copy; P = 8.15 × 10−8). A candidate gene analysis suggested that CYP2C9*2 also affects the AUC of both fluvastatin enantiomers and that SLCO2B1 single‐nucleotide variations may affect the AUC of 3S,5R‐fluvastatin. Thus, SLCO transporters have enantiospecific effects on fluvastatin pharmacokinetics in humans. Genotyping of both CYP2C9 and SLCO1B1 may be useful in predicting fluvastatin efficacy and myotoxicity.

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Section: Discussionmentioning

confidence: 99%

“…Fluvastatin is a 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitor, which is used in the treatment of hypercholesterolemia. It is a racemic mixture of two enantiomers, of which 3R,5S‐fluvastatin is 30 times more active than 3S,5R‐fluvastatin . Fluvastatin is extensively metabolized via cytochrome P450 (CYP) 2C9 .…”

mentioning

confidence: 99%

Enantiospecific Pharmacogenomics of Fluvastatin

Hirvensalo

Tornio

Neuvonen

et al. 2019

Clin Pharma and Therapeutics

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“…3 -7 Currently, 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors are widely used to treat hyperlipidaemia, but there are few reports on the use of HMG-CoA reductase inhibitors in hyperlipidaemia patients undergoing HD. 8 -10 This study investigates the effect of fluvastatin, a totally synthetic HMG-CoA reductase inhibitor, 11 on serum lipid levels, as well as the effect of HD on fluvastatin plasma concentrations.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Lipid-Lowering Effect of Fluvastatin in Hypercholesterolaemic Patients on Maintenance Haemodialysis

et al. 2004

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Patients undergoing haemodialysis are predisposed to serum lipid abnormalities that can accelerate the development of atherosclerosis. Serum lipid levels must therefore be controlled over a long period. For patients with reduced renal function (including dialysis patients), special attention must be paid to hyperlipidaemia therapy, particularly drug selection. In this study, 30 mg/day fluvastatin was administered orally to five patients receiving maintenance haemodialysis. Their serum lipid levels and blood biochemistry were monitored during the 6 months of fluvastatin administration, and the pharmacokinetic parameters calculated. The therapeutic efficacy and safety of fluvastatin were demonstrated in this patient group. Furthermore, fluvastatin is not influenced by the dialysis membrane and does not accumulate in haemodialysis patients with hyperlipidaemia.

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“…The pharmacokinetic and pharmacodynamic properties of fluvastatin are not modified by age or sex (12). In controlled clinical trials in young and middle-aged patients with primary hypercholesterolemia, fluvastatin, at a dose of 20 to 80 mg once daily, reduced the LDL-C, TG, and apolipoprotein B (apo B) by 22 to 36%, 12 to 18%, and 19 to 23%, respectively (13,14).…”

Section: Introductionmentioning

confidence: 99%

Lipid-lowering response of the HMG-CoA reductase inhibitor fluvastatin is influenced by polymorphisms in the low-density lipoprotein receptor gene in Brazilian patients with primary hypercholesterolemia

Salazar¹,

Hirata²,

Quintão³

et al. 2000

J. Clin. Lab. Anal.

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Although the efficacy of fluvastatin (HMG-CoA reductase inhibitor) in the treatment of primary hypercholesterolemia is well documented, a wide interindividual variation treatment response has been observed. We have studied the possible role of the AvaII (exon 13), HincII (exon 12), and PvuII (intron 15) polymorphisms at the low-density lipoprotein receptor (LDLR) gene on lipid-lowering response in 55 patients (36 to 70 years old) with primary hypercholesterolemia treated with fluvastatin for 16 weeks. LDLR genotypes were determined by PCR-RFLP. The results indicate that the AvaII and PvuII polymorphisms influence the cholesterol-lowering response of the HMG-CoA reductase inhibitor Fluvastatin. Patients carrying A+A+ (AvaII) or P1P1 (PvuII) homozygous genotypes presented lower reduction in total cholesterol, LDL-C and apolipoprotein B levels after 16 weeks of treatment with fluvastatin, when compared to other genotypes (P<0.05). Our data also support the previous assumption that the AvaII, HincII, and PvuII polymorphisms of the LDLR gene are associated with variation of serum cholesterol levels. Therefore, the identification of the LDLR genetic profile may provide better prediction of a patient's clinical response to fluvastatin.

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HMG‐CoA Reductase Inhibitors: An Exciting Development in the Treatment of Hyperlipoproteinemia

Cited by 104 publications

References 25 publications

Enantiospecific Pharmacogenomics of Fluvastatin

Enantiospecific Pharmacogenomics of Fluvastatin

Pharmacokinetics and Lipid-Lowering Effect of Fluvastatin in Hypercholesterolaemic Patients on Maintenance Haemodialysis

Lipid-lowering response of the HMG-CoA reductase inhibitor fluvastatin is influenced by polymorphisms in the low-density lipoprotein receptor gene in Brazilian patients with primary hypercholesterolemia

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