Pravastatin Sodium, an Inhibitor of HMG-CoA Reductase, Decreases HDL Cholesterol by Transfer of Cholesteryl Ester from HDL to VLDL in Japanese White Rabbits

Miyazaki, A.; Koieyama, Tadashi; Shimada, Yukio; Kikuchi, Takashi; Ito, Kayoko; Kasanuki, Naomi; Koga, Tetsufumi

doi:10.5551/jat.11.22

Cited by 6 publications

(3 citation statements)

References 21 publications

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“…Moreover, as we did not have a concurrent control group that was not on pravastatin, we cannot determine the effect of pravastatin in contributing to the abnormalities in the HDL‐Chol nor its effect on either of the two lipid ratios, although none of the previous adult studies have found an impact on HDL‐Chol with the statins. There are, however, several animal studies in which pravastatin has been shown to decrease HDL‐Chol levels (47, 48). The mechanism by which it does so is not clear, but it may be related to the transfer of cholesterol esters from HDL to VLDL particles.…”

Section: Discussionmentioning

confidence: 99%

Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantation

Butani

2005

Pediatric Transplantation

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Hyperlipidemia is common after renal transplantation (Tx) and contributes to the increased cardiovascular morbidity seen in the post-transplant period. Limited data are available on the utility of the statins in children after renal Tx. This 12-month prospective study was undertaken to determine the efficacy of pravastatin in reducing dyslipidemia after renal Tx in children and to determine predictors of dyslipidemia after Tx. From August 2001 to April 2004, all 17 newly transplanted pediatric renal transplant recipients at our center were preemptively treated with pravastatin from the immediate post-transplant period. Fasting lipid profiles were obtained at 1, 3, 6 and 12 months after Tx. Trends in the lipid profile were analyzed using the repeated measures general linear model (GLM). A historical cohort of pediatric renal-transplant recipients not treated with pravastatin was used as the control population. The mixed effects GLM was used for multivariable logistic regression analyses to determine the independent effect of age, pretransplant cholesterol (Chol), body mass index (BMI), creatinine clearance (CrCl), and corticosteroid and tacrolimus doses on the development of dyslipidemia. The mean age of the children at Tx was 8.7 yr. The GLM analysis showed that with time, there was a significant decline in the total Chol, serum triglyceride (TG), LDL and also HDL-Chol (p-value <0.05 for each). Compared with the controls, the mean serum Chol was lower at all time points post-transplant in the treated patients. However, despite treatment, the prevalence of hypercholesterolemia increased from 31% pretransplant to 53% at 1-month, but declined thereafter to 6% at 3 and 6 months and 0% at 1 yr. Multivariable regression analyses showed the prednisone dose, pretransplant Chol and age to be the most important risk factors for the development of dyslipidemia. No child developed complications related to therapy. In summary, pravastatin is safe in the post-transplant period in children and reduces serum Chol, LDL-Chol and TG. An unexpected finding in our study was the decline in HDL-Chol after Tx. Whether the preemptive use of the statins will result in lower cardiovascular morbidity, especially considering the concomitant reduction in HDL-Chol remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantation

Butani

2005

Pediatric Transplantation

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“…Although the series 9-17 did not increase the HDL-cholesterol content, an effect that would promote reverse cholesterol transport and other antiatherogenic effects [Meyers and Kashyap, 2004], their hypolipidemic potential is not necessary compromised, because some of the clinically used hypolipidemic drugs such as pravastatin [Miyazaki et al, 2004] and probucol [Tikkanen et al, 1987;Doggrell, 2003], or even compounds 1 and 2 (Table 3), do not exhibit such effect either.…”

Section: Discussionmentioning

confidence: 99%

Design of new potent hypolipidemic agents with the synergistic structural properties of α‐asarone and fibrates

Zúñiga¹,

Garduño‐Siciliano²,

Cruz³

et al. 2005

Drug Development Research

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The series of bioisosteric analogs 9-17 were designed based on the potential pharmacophores of the highly hypolipidemic agents, a-asarone (1), and fibrates such as clofibrate (2) and fenofibrate (3). These compounds are characterized by their simplicity, in terms of functional group diversity, because most of them are phenoxyacetic acids or their methyl and ethyl esters monosubstituted by an ethyl side-chain at the ortho, meta, and para positions of the benzene ring. Despite this structural simplicity, these derivatives exhibited potent hypocholesterolemic activity, lowering the mice serum cholesterol and low-density lipoprotein cholesterol levels up to 40% at the lowest dose of 25 mg/kg. These results supported the concept that the phenoxyacetic frame and the ethyl side-chain can be considered as potent pharmacophores for the preparation of potential hypocholesterolemic drugs. Drug Dev. Res. 64:28-40, 2005.

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“…However, we did observe that triglycerides continued to be elevated in the treated children (15% at 1 yr) and that the HDL cholesterol declined in the treated population over time. While the fall in HDL cholesterol can likely be explained by changes in renal function and reduction in steroid dose over time, the possibility that some of this effect may be due to the pravastatin itself cannot be entirely ruled out as in some animal models a similar effect of pravastatin has been seen (38). Our current strategy has been to use a steroid‐minimization protocol and in addition pre‐ emptively use pravastatin in all children, and with this approach, we have seen an even lower incidence of dyslipidemia (L. Butani, personal communication).…”

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confidence: 99%

Dyslipidemia after renal transplantation: A cause for concern?

Butani

2008

Pediatric Transplantation

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Pravastatin Sodium, an Inhibitor of HMG-CoA Reductase, Decreases HDL Cholesterol by Transfer of Cholesteryl Ester from HDL to VLDL in Japanese White Rabbits

Cited by 6 publications

References 21 publications

Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantation

Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantation

Design of new potent hypolipidemic agents with the synergistic structural properties of α‐asarone and fibrates

Dyslipidemia after renal transplantation: A cause for concern?

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