Effect of morning versus evening intake of simvastatin on the serum cholesterol level in patients with coronary artery disease

Lund, Tor M; Torsvik, Harald; Falch, D. K.; Christophersen, Berit; Skårdal, Rita; Gullestad, Lars

doi:10.1016/s0002-9149(02)02614-0

Cited by 30 publications

(20 citation statements)

References 11 publications

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“…F105 was dosed at 2 capsules (total 500 mg BFE and 220 mg phytocomplex blend). Subjects were instructed to take the daily dose at dinnertime as clinical studies indicate greater efficacy of HMG-CoA reductase inhibitors with evening dosing (Lund et al 2002;Wallace et al 2003). Clinical visits took place at weeks 0, 4, 8, and 12 with one electronic Visit Questionnaire between the 4-and 8-week clinical visits.…”

Section: Study Proceduresmentioning

confidence: 99%

Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation includingCitrus bergamia, in subjects with moderate cardiometabolic risk factors

Babish¹,

Dahlberg

et al. 2016

Can. J. Physiol. Pharmacol.

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Abstract:We examined the clinical safety and efficacy of F105 in 11 subjects with moderate dyslipidemia. F105 is a combination of bergamot fruit extract (Citrus bergamia, BFE) and 9 phytoextracts selected for their ability to improve the antioxidant and anti-inflammatory activity of BFE. In vitro F105 exhibited a synergistic inhibition of oxygen radical absorbing capacity, peroxynitrite formation, and myeloperoxidase activity. Following 12 weeks of F105 daily, no treatment-related adverse events or changes in body mass were seen. Statistically significant changes were noted in total cholesterol (−7.3%), LDL-cholesterol (−10%), non-HDL cholesterol (−7.1%), cholesterol/HDL (−26%), and apolipoprotein B (−2.8%). A post hoc analysis of 8 subjects with HbA1c > 5.4 and HOMA-IR score > 2 or elevated triglycerides revealed additional statistically significant changes in addition to those previously observed in all subjects including triglycerides (−27%), oxLDL (−19%), LDL/HDL (−25%), triglycerides/HDL (−27%), oxLDL/HDL (−25%), and PAI-1 (−37%). A follow-up case report of a 70-year-old female patient, nonresponsive to statin therapy and placed on F105 daily, demonstrated improved cardiometabolic variables over 12 weeks similar to the subgroup. In summary, F105 was clinically well-tolerated and effective for ameliorating dyslipidemia in subjects with moderate cardiometabolic risk factors, particularly in the individuals with HbA1c > 5.4%.Key words: cardiometabolic disease, bergamot, antioxidant, myeloperoxidase, oxidized LDL, dyslipidemia, HbA1c. Résumé :Les auteurs ont examiné la sécurité et l'efficacité cliniques du F105 chez 11 sujets présentant une dyslipidémie modérée. Le F105 est une combinaison d'extrait de bergamote (Citrus bergamia, EB) et 9 extraits végétaux sélectionnés pour leur capacité à améliorer l'activité antioxydante et anti-inflammatoire de l'EB. In vitro, le F105 montrait une inhibition synergique de la capacité d'absorption des radicaux d'oxygène, de formation de peroxynitrite et de l'activité myéloperoxydase. Après 12 semaines d'administration quotidienne de F105, aucun effet secondaire indésirable relié au traitement ou changements de poids corporels n'étaient observés. Des changements statistiquement significatifs ont été notés quant au cholestérol total (−7,3 %), LDL-cholestérol (−10 %), non-HDL-cholestérol (−7,1 %), cholestérol/HDL (−26 %) et apolipoprotéine B (−2,8 %). Une analyse post hoc de 8 sujets présentant une HbA1c > 5.4 et un indice HOMA-IR >2 ou des triglycérides élevés a révélé des changements additionnels statistiquement significatifs en plus de ceux précédemment observés chez tous les sujets incluant les triglycérides (−27 %), oxLDL (−19 %), LDL/HDL (−25 %) triglycérides/HDL (−27 %), oxLDL/HDL (−25 %), et PAI-1 (−37 %). Une étude de cas de suivi d'une patiente de 70 ans, ne répondant pas à la thérapie par les statines et traitée au F105 quotidiennement, a démontré amélioration des variables cardiométaboliques pendant les 12 semaines similaire au sous-groupe. En résumé, le F105 est bie...

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Section: Study Proceduresmentioning

confidence: 99%

Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation includingCitrus bergamia, in subjects with moderate cardiometabolic risk factors

Babish¹,

Dahlberg

et al. 2016

Can. J. Physiol. Pharmacol.

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“…The results of three published clinical trials suggest that LDL reduction may be greater in patients taking simvastatin in the evening compared to the morning [6,27,28]. Saito et al [27] compared the reduction in LDL from baseline after morning and evening administration of simvastatin 2.5 and 5 mg doses.…”

Section: Discussionmentioning

confidence: 99%

“…The remaining differences at week 4 (2.5 mg), week 8 (5 mg), week 12 (2.5 and 5 mg) were not statistically significant. Lund et al [6] performed a small (n = 25) randomized crossover trial in patients taking simvastatin 10-40 mg daily. LDL plasma concentrations were found to be 2.8 mmol ⁄ L after evening dosing and 2.5 mmol ⁄ L when taken in the morning.…”

Section: Discussionmentioning

confidence: 99%

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The Influence of Dosing Time, Variable Compliance and Circadian Low-Density Lipoprotein Production on the Effect of Simvastatin: Simulations from a Pharmacokinetic-Pharmacodynamic Model

Wright

Kumar

Al‐Sallami

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

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The aim of this study was to explore the influence of simvastatin dosing time, variable compliance and circadian cholesterol production on the reduction of low-density lipoprotein (LDL). A published pharmacokinetic-pharmacodynamic (PKPD) model for simvastatin was identified and evaluated. A model for circadian LDL production was incorporated into the PKPD model. Reduction in LDL from baseline was simulated stochastically from the full model at dose levels of 10, 20, 40 and 80 mg daily for 30 days. Simulated dosing times for each data set were morning (8.00 a.m.), evening (22.00 p.m.), evening with reduced compliance and evening for a hypothetical bioequivalent generic. Differences in LDL reduction from baseline between evening (33-43%) and morning dosing (31-43%) were negligible across a range of doses. Any differences were negated when variable compliance was considered. In addition, differences in simvastatin effect between morning and evening dosing were found to be within the range of LDL concentrations that would be permissible for a bioequivalent generic (at the lower limit) and hence are not likely to be important clinically. The results of this study suggest that taking simvastatin in the evening is not superior to morning dosing.Elevated plasma low-density-lipoprotein (LDL) concentrations have been linked to an increased risk of cardiovascular and cerebrovascular morbidity and mortality [1,2]. It has been proposed that a reduction in plasma LDL by 1 mmol ⁄ L will result in about a 20% reduction in adverse vascular events, regardless of the baseline concentration [3]. This would represent a 25-35% reduction in LDL concentration from a baseline of 3-4 mmol ⁄ L. Simvastatin reduces serum LDL concentrations by inhibiting HMG-CoA reductase, the rate-limiting enzyme for cholesterol production in the liver.Cholesterol synthesis follows a circadian pattern, with peak production occurring between midnight and 6.00 a.m. [4,5]. It is usually recommended that daily doses of simvastatin be taken in the evening on the grounds that this will allow peak simvastatin concentrations to occur at the same time as peak circadian cholesterol production [6][7][8][9]. Hence, it is generally assumed that evening dosing will result in a greater reduction in plasma LDL compared with morning dosing. However, the rate-limiting step in the time course of simvastatin effect on cholesterol is not the half-life of simvastatin but the relatively slow turnover of cholesterol itself. The estimated half-life of cholesterol in the plasma is in the order of 3-4 days [9]. As a result, the peak effect of simvastatin on LDL reduction has been found to be substantially delayed with respect to the peak plasma concentration of the drug [10,11]. This suggests that dosing simvastatin in the evening and measuring LDL in the morning may not necessarily reflect the greatest effect on plasma cholesterol concentrations.Compliance with evening dosing has been found to be 5-25% lower compared with morning dosing for a variety of cardiovascular dru...

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“…In a randomized, crossover study in patients with coronary artery disease (n = 25), TC and LDL-C were 7.3% (p = 0.002) and 13.4% (p < 0.001) higher, respectively, in patients receiving simvastatin, 10–40 mg/day, in the morning compared with patients receiving the same dose administered in the evening [23]. Morning and evening administration of simvastatin were also compared in a randomized study involving 60 patients already receiving simvastatin, 10–20 mg, in the evening for primary or secondary prevention of coronary heart disease, stroke or peripheral vascular disease.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Fluvastatin-Extended Release in Hypercholesterolemic Patients: Morning Administration Is Equivalent to Evening Administration

et al. 2006

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Background: Flexibility in the time of administration of statin therapy is likely to improve patient compliance. This study compared the efficacy and tolerability of morning and evening administration of the extended-release formulation of fluvastatin (fluvastatin XL). Methods: In this prospective, double-blind, multicenter, multiple dose study, 236 patients with type IIa/b hypercho lesterolemia were randomized to receive fluvastatin XL, 80 mg, in the morning or evening for 8 weeks. Results: At 8 weeks, low-density lipoprotein cholesterol levels were reduced by 34.5 and 35.0% in the morning and evening treatment groups, respectively (p = 0.0118 for non-inferiority of morning administration). There were no statistically significant differences between the morning and evening treatment groups in the changes in total cholesterol (p = 0.56), high-density lipoprotein cholesterol (p = 0.21), triglycerides (p = 0.13), apolipoprotein B (p = 0.66) and apolipoprotein AI (p = 0.88) at 8 weeks. The frequency of adverse events was slightly lower in the morning treatment group compared with the evening treatment group (27.4 vs. 35.5%). Conclusions: The efficacy and safety profiles of fluvastatin XL are equivalent for morning and evening administration.

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Effect of morning versus evening intake of simvastatin on the serum cholesterol level in patients with coronary artery disease

Cited by 30 publications

References 11 publications

Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation includingCitrus bergamia, in subjects with moderate cardiometabolic risk factors

Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation includingCitrus bergamia, in subjects with moderate cardiometabolic risk factors

The Influence of Dosing Time, Variable Compliance and Circadian Low-Density Lipoprotein Production on the Effect of Simvastatin: Simulations from a Pharmacokinetic-Pharmacodynamic Model

Efficacy and Safety of Fluvastatin-Extended Release in Hypercholesterolemic Patients: Morning Administration Is Equivalent to Evening Administration

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