Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia

Hedman, Mia; Neuvonen, Pertti J.; Neuvonen, Mikko; Antikainen, Marjatta

doi:10.1016/s0009-9236(03)00153-x

Cited by 33 publications

(39 citation statements)

References 26 publications

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“…Statins were associated with increased alanine aminotransaminase and/or aspartate aminotransferase levels in some, 168,187,203,206 but not all, 18,164,202,204 of these studies. Reports of elevated creatine kinase levels were similarly conflicting.…”

Section: Drug Treatmentmentioning

confidence: 79%

Screening and Treatment for Lipid Disorders in Children and Adolescents: Systematic Evidence Review for the US Preventive Services Task Force

et al. 2007

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Section: Drug Treatmentmentioning

confidence: 79%

Screening and Treatment for Lipid Disorders in Children and Adolescents: Systematic Evidence Review for the US Preventive Services Task Force

et al. 2007

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“…Twenty four hours later subjects received a second 40 mg dose, again in the presence of an investigator, and 1.5 hours later, a time when peak concentrations of pravastatin are expected to occur, 50 mL blood was drawn. Several studies have shown that the mean time to reach maximum concentration of pravastatin is approximately 1.5 hours (range, 0.5–4 hours) [15], thus we drew blood for the ex vivo studies 1.5 hours after administration of pravastatin.…”

Section: Methodsmentioning

confidence: 99%

Effects of C‐reactive Protein and Homocysteine on Cytokine Production: Modulation by Pravastatin

Asanuma

Oeser²,

Stanley³

et al. 2008

Archives of Drug Info

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ObjectiveC-reactive protein (CRP) and homocysteine are markers of cardiovascular risk that may have inflammatory effects. HMG coenzyme A reductase inhibitors (statins) have anti-inflammatory effects in vitro, but it is not clear if such responses in vivo are secondary to lipid lowering. We examined the hypothesis that CRP and homocysteine would stimulate cytokine release in human whole blood and that short-term treatment with a statin would inhibit it.MethodsThe time course of IL-6 and MCP-1 production was determined in whole blood incubated with saline, 1 µg/mL lipopolysaccaride (LPS), 50 and 100 µM/L DL-homocysteine, and 5 µg/mL human recombinant CRP for 24 hours at 37°C under 5% CO2 atmosphere. Cytokine responses were determined in blood drawn from 15 healthy volunteers before and after administration of pravastatin 40 mg daily for 2 days.ResultsBoth human recombinant CRP and LPS significantly increased the production of IL-6 and MCP-1 in whole blood samples more than 4-fold (P < 0.001) but homocysteine did not. Oral administration of pravastatin, 40mg daily for 2 days, decreased CRP-stimulated IL-6 production by approximately 20% (P = 0.02) 6 hours after incubation, but did not affect MCP-1 production (P = 0.69). Pravastatin treatment did not affect LPS-stimulated MCP-1 but increased IL-6 modestly.ConclusionsCRP stimulated the production of the proatherogenic mediators MCP-1 and IL-6 in human whole blood, but homocysteine did not. CRP-stimulated production of IL-6, but not MCP-1, was modestly attenuated by short-term treatment with pravastatin.

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“…Simvastatin, introduced in the early 1990s, is also a lipophilic, semi-synthetic inhibitor of HMG-CoA reductase and administered as an inactive lactone prodrug that undergoes carboxylesterase-mediated conversion in the plasma, liver and intestine to simvastatin acid, which is the active metabolite 40 . Pravastatin, introduced in the early 1990s, is a hydrophilic, semi-synthetic inhibitor of HMG-CoA reductase 41 . Due to its hydrophilic nature, it fails to cross the blood brain barrier, making it a potentially safer alternative for maturing brains in children.…”

Section: Evolution Of Statin Therapy In Childrenmentioning

confidence: 99%

Pediatric Pharmacogenomics

Wagner¹,

Leeder²

2012

Pediatric Clinics of North America

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Synopsis The dose-exposure-response relationship for drugs may differ in pediatric patients compared to adults due to developmental changes in processes involved in drug disposition (absorption, distribution, metabolism and excretion) and drug response. This relative knowledge deficit has complicated drug efficacy and safety labeling of drugs for pediatric use. With the legislative changes that have occurred in the US and Europe over the last 20 years, many clinical studies have been conducted to establish drug dose-exposure relationships across the pediatric age spectrum from birth to adolescence. However, genetic variation has seldom been included in these investigations. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

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Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia

Cited by 33 publications

References 26 publications

Screening and Treatment for Lipid Disorders in Children and Adolescents: Systematic Evidence Review for the US Preventive Services Task Force

Screening and Treatment for Lipid Disorders in Children and Adolescents: Systematic Evidence Review for the US Preventive Services Task Force

Effects of C‐reactive Protein and Homocysteine on Cytokine Production: Modulation by Pravastatin

Pediatric Pharmacogenomics

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