4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Pharmacodynamic effects and pharmacokinetics of a new HMG-CoA reductase inhibitor, rosuvastatin, after morning or evening administration in healthy volunteers.

      British Journal of Clinical Pharmacology

      Absorption, Administration, Oral, Adult, Area Under Curve, Cross-Over Studies, Dose-Response Relationship, Drug, Female, Fluorobenzenes, administration & dosage, pharmacokinetics, pharmacology, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, blood, Male, Middle Aged, Pyrimidines, Sulfonamides, Time Factors

      Read this article at

      ScienceOpenPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          To compare the lipid-regulating effects and steady-state pharmacokinetics of rosuvastatin, a new synthetic hydroxy methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, following repeated morning and evening administration in volunteers with fasting serum low-density lipoprotein cholesterol (LDL-C) concentrations < 4.14 mmol l-1. In this open-label two-way crossover trial 24 healthy adult volunteers were randomized to receive rosuvastatin 10 mg orally each morning (07.00 h) or evening (18.00 h) for 14 days. After a 4 week washout period, volunteers received the alternative regimen for 14 days. Rosuvastatin was administered in the absence of food. Reductions from baseline in serum concentrations of LDL-C (-41.3%[morning]vs-44.2%[evening]), total cholesterol (-30.9%vs-31.8%), triglycerides (-17.1%vs-22.7%), and apolipoprotein B (-32.4%vs-35.3%) were similar following morning and evening administration. AUC(0,24 h) for plasma mevalonic acid (MVA), an in vivo marker of HMG-CoA reductase activity, decreased by -29.9% (morning) vs-32.6% (evening). Urinary excretion of MVA declined by -33.6% (morning) vs-29.2% (evening). The steady-state pharmacokinetics of rosuvastatin were very similar following the morning and evening dosing regimens. The Cmax values were 4.58 vs 4.54 ng ml-1, and AUC(0,24 h) values were 40.1 vs 42.7 ng ml-1 h, following morning and evening administration, respectively. There were no serious adverse events during the trial, and rosuvastatin was well tolerated after morning and evening administration. The pharmacodynamic effects and pharmacokinetics of rosuvastatin are not dependent on time of dosing. Morning or evening administration is equally effective in lowering LDL-C.

          Related collections

          Most cited references 7

          • Record: found
          • Abstract: found
          • Article: not found

          Systematic review on the risk and benefit of different cholesterol-lowering interventions.

          Meta-analyses have investigated the efficacy of cholesterol-lowering interventions in relation to the underlying risk of coronary heart disease and the extent and duration of cholesterol reduction. We systematically reviewed the efficacy of antilipidemic interventions on major mortality outcomes in relation to drug classes. We searched MEDLINE and EMBASE from 1966 through October 1996 for randomized, controlled trials of any cholesterol-lowering interventions reporting mortality data. We included 59 trials involving 85 431 participants in the intervention and 87 729 participants in the control groups. We pooled these trials into 7 pharmacological categories of cholesterol-lowering interventions: statins (13 trials), fibrates (12 trials), resins (8 trials), hormones (8 trials), niacin acid (2 trials), n-3 fatty acids (3 trials), and dietary interventions (16 trials). Of the cholesterol-lowering interventions, only statins showed a large and statistically significant reduction in mortality from coronary heart disease (risk ratio, 0.66; 95% confidence interval [CI], 0.54 to 0. 79) and from all causes (risk ratio, 0.75; 95% CI, 0.65 to 0.86). For both all-cause and cardiovascular mortality, the difference between statins and the combined estimate of the other classes of agents was unlikely to be due to chance (P<0.02 for both comparisons). Meta-regression analysis demonstrated that variability in results across trials could be largely explained on the basis of differences in the magnitude of cholesterol reduction. Statins have the largest effect on the reduction of cardiovascular and all-cause mortality, and this result recommends their use in preference to other antilipidemic agents. The greater effect of statins is likely due to the larger reduction in cholesterol.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            No effect of age or gender on the pharmacokinetics of rosuvastatin: a new HMG-CoA reductase inhibitor.

            The effects of age and gender on the pharmacokinetics of rosuvastatin (Crestor) were assessed in healthy young (18-35 years) and elderly (> 65 years) males and females in this open, nonrandomized, noncontrolled, parallel-group trial. Sixteen males and 16 females (8 young and elderly volunteers per gender group) were enrolled. Mean (range) ages were 24 (18-33) and 68 (65-73) years for young and elderly volunteers, respectively. Volunteers were given a single oral 40 mg dose of rosuvastatin. Blood samples for measurement of rosuvastatin plasma concentration were collected up to 96 hours following dosing. Age and gender effects were assessed by constructing 90% confidence intervals (CIs) around the ratios of young/elderly and male/female geometric least square means (glsmeans) for AUC(0-t) and Cmax (derived from ANOVA of log-transformed parameters). Small differences in rosuvastatin pharmacokinetics were noted between age and gender groups. Glsmean AUC(0-t) was 6% higher (90% CI = 0.86-1.30) and glsmean Cmax, 12% higher (90% CI = 0.83-1.51) in the young compared with the elderly group. Glsmean AUC(0-t) was 9% lower (90% CI = 0.74-1.12) and glsmean Cmax 18% lower (90% CI = 0.61-1.11) in the male compared with the female group. These small differences are not considered clinically relevant, and dose adjustments based on age or gender are not anticipated. Rosuvastatin was well tolerated in all volunteers.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening.

              The pharmacodynamic effects and pharmacokinetics of atorvastatin, a potent investigational inhibitor of HMG-CoA reductase, were studied in 16 normolipidemic subjects after administration of 40 mg daily for 15 days in the morning or evening. Lipid and apolipoprotein parameters were determined, and plasma atorvastatin equivalent concentrations were measured according to a validated enzyme inhibition bioassay procedure. Atorvastatin was well tolerated by the participants. Overall, mean reductions of 34% in total cholesterol, 48% in low-density lipoprotein (LDL) cholesterol, 37% in very low density lipoprotein (VLDL) cholesterol, 25% in triglycerides, 6% in apolipoprotein A-I, and 34% in apolipoprotein B were observed. Changes in lipid and apolipoprotein values were similar after morning and evening administration of atorvastatin. In contrast, studies with other HMG-CoA reductase inhibitors have consistently shown that evening administration results in larger reductions in total and LDL cholesterol than does morning administration. Rate and extent of equivalent absorption of atorvastatin were lower during evening than morning administration. Mean elimination half-life values were similar, however, suggesting that there is no diurnal variation in disposition of this drug. Pharmacokinetic differences did not correlate with effects on serum lipids.
                Bookmark

                Author and article information

                Journal
                12445025
                1874466

                Comments

                Comment on this article