Abnormalities of Ion Transport in Hypercholesterolemia and Hypertriglyceridemia: A Link with Essential Hypertension?
Antonio Coca, Ricardo P. Garay in Ionic Transport in Hypertension: New Perspectives, 2019
In a similar study, Weder et al.32 used lovastatin to reduce cholesterol in patients with elevated cholesterol, but normal triglycerides. After 24 weeks in the double-blind, randomized trial, total cholesterol and LDL cholesterol were significantly decreased and HDL cholesterol was increased. Triglycerides were somewhat reduced (p = 0.10). However, there were no significant changes in Na-Li counter-transport, Na-K cotransport, passive Li efflux, or cellular water content. Na content was reduced as was amiloride-sensitive platelet volume response to cellular acidification. This study tends to support the notion that changes in cholesterol are only mildly, if at all, related to changes in Na-Li countertransport. The change in triglycerides seems to be the most important controlling factor, and triglycerides were only somewhat reduced in this study.
Natural Polyketides to Prevent Cardiovascular Disease
Catherina Caballero-George in Natural Products and Cardiovascular Health, 2018
Shortly after the isolation of mevastatin, another potent HMGR inhibitor was discovered by Dr. Albert Chen. Once again supporting the value of polyketides as a source of novel compounds, lovastatin, was isolated from another fungi, Aspergillus terreus (Alberts et al., 1980). Over the course of the next several years, between 1980 and 1987, mevastatin would eventually be removed from clinical trials and lovastatin would take its place as the leading drug candidate, showing marked reductions of low-density lipoprotein (LDL) cholesterol and no significant adverse side effects in short-term animal trials. Despite initial concerns, in 1987 the US FDA approved lovastatin due to its impressive reduction of apolipoprotein-B-containing lipoproteins and plasma triglycerides paired with increases of high-density lipoproteins (HDL). Lovastatin was introduced as a means for addressing cholesterol levels other than by dietary modifications.
Efavirenz
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Most HMG-CoA reductase inhibitors (statins) are metabolized by either CYP3A4 (atorvastatin, lovastatin, and simvastatin) or CYP2C9 (fluvastatin and rosuvastatin) (Shitara and Sugiyama, 2006), except pravastatin, which is predominantly metabolized by glucuronidation (Fichtenbaum and Gerber, 2002). Efavirenz induces the metabolism of simvastatin, atorvastatin, and pravastatin, reducing the AUC0–24 of these agents by 58%, 43%, and 40%, respectively (Gerber et al., 2005); if these agents are used with efavirenz, cholesterol levels should be monitored, and the statin dosage adjusted accordingly. Lovastatin has not been studied, but would be expected to behave in a similar fashion. Rosuvastatin is largely excreted unchanged in the feces, and no interaction with efavirenz would be anticipated.
Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs
Published in Drug Metabolism Reviews, 2023
Amina Džidić-Krivić, Jasna Kusturica, Emina Karahmet Sher, Nejra Selak, Nejra Osmančević, Esma Karahmet Farhat, Farooq Sher
Statins are widely prescribed drugs and have been used for years, however yet the considerable individual variation in therapeutic response remains one of the main problems in statins therapy. Genetics is only one small part of this variability (Yoo et al. 2014). Lovastatin and simvastatin can be taken as an example. Yoo et al. (2014) investigated on rats how gut microbiota involved in lovastatin metabolism, particularly focusing on its biotransformation to one of the important lovastatin metabolites, the active hydroxy-acid metabolite (M8). The authors compared how the profile of lovastatin and its metabolites concentration, especially M8 changes in plasma, after the oral administration of this drug. Two groups of animals were used. The control group of rats has not been administered with antibiotics. On the other hand, the experimental group of rats have been treated with antibiotics such as ampicillin or they have been treated with a mixture of antibiotics, containing erythromycin, cefadroxil and oxytetracycline. Pharmacokinetic analyses showed an experimental group of rats had significantly lower levels of systemic exposure to lovastatin metabolite M8 as opposed to the control group of rats. The resulting pharmacokinetic parameters suggested that the formation of lovastatin active metabolite M8 is effected by the enzymes produced by gut microbiota (Yoo et al. 2014).
Neuroinflammation and oxidative stress in schizophrenia: are these opportunities for repurposing?
Published in Postgraduate Medicine, 2022
Zarrin Ansari, Sudhir Pawar, Rajmohan Seetharaman
Simvastatin versus placebo adjunct therapy to risperidone was evaluated in 66 patients over 8 weeks. The simvastatin group demonstrated more significant improvement in negative symptoms than the placebo group. However, there was no significant difference seen in the positive symptoms and the psychopathology scores [94]. Chaudhary et al., Vincenzi et al. and Sayyah et al. evaluated various statins as adjunctive therapy. Trends toward improvement were seen in all the studies; however, the difference was not significant versus the placebo group [95,96]. A meta-analysis by Shen et al. involved six RCTs with 339 participants (169 on antipsychotics and statins versus 170 on placebo). The results clarified that adjunct therapy with statins improved the psychotic symptoms (either negative or positive) of SCZ [97]. No significant improvement was observed between lovastatin versus placebo treatment in an 8-week trial conducted by Ghanizadeh et al. [98]
Advances with lipid-lowering drugs for pediatric patients with familial hypercholesterolemia
Published in Expert Opinion on Pharmacotherapy, 2021
Filipe Ferrari, Vítor M. Martins, Viviane Z. Rocha, Raul D. Santos
Table 2 shows US FDA approved doses upon LDL-C of the most frequently used statins and ezetimibe in pediatric FH patients. Lovastatin is approved by the U.S. Food and Drug Administration (FDA) for use in children with heterozygous FH ≥10 years old, followed by simvastatin, atorvastatin, fluvastatin, and rosuvastatin; pravastatin is approved for use in patients as young as 8 years of age. In children from 6 years old, rosuvastatin is approved in Europe, while atorvastatin is approved in Australia [4]. It is not recommended to adjust the dose of statins based on body weight, but it is advised to start with low doses, with up-titration based on LDL-C levels [50]. However, it is important to notice that the highest doses of potent statins for children, like atorvastatin and rosuvastatin, are, respectively, a quarter and half the ones approved for adults, so patients may not benefit from maximal effect of these medications especially with atorvastatin.
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