Objective: The aim of the study was to compare the efficacy/safety of doubling the dose of low-, medium- and high-potency statins on lipids/lipoproteins versus ezetimibe/simvastatin (EZE/SIMVA) 10/40 mg in patients with a recent coronary event. Methods: In this open-label study, patients were stratified by baseline statin therapy (low, medium and high potency) and randomized equally to statin dose doubling or EZE/SIMVA 10/40 mg for 12 weeks. Primary analysis concerned change in low-density lipoprotein cholesterol for the whole population. Treatment-by-stratum interaction evaluated the consistency of treatment effect across statin potency strata. Post hoc analysis of between-group efficacy within strata was performed using ANCOVA. Results: Within each stratum, EZE/SIMVA produced significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and non-high-density lipoprotein cholesterol (HDL-C) compared to statin doubling. Numerical trends toward smaller between-group reductions were observed with higher-potency statins and reached statistical significance for apolipoprotein B and non-HDL-C. No significant between-group differences in HDL-C and C-reactive protein were observed within each stratum. EZE/SIMVA produced larger reductions in triglycerides versus low-potency statin, whereas it was similarly effective compared with intermediate-/high-potency statins. The safety/tolerability profiles of the treatments were similar across the strata. Conclusions: EZE/SIMVA 10/40 mg produced greater improvements in lipids with a similar safety profile compared to doubling the dose of low-, medium- and high-potency statins.

Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for the treatment of major depressive disorder, is extensively hepatically metabolized. The pharmacokinetics, tolerability, and safety of vilazodone were investigated in 2 trials comparing participants with hepatic impairment with healthy controls. In these phase 1, open-label, parallel-group, single-dose pharmacokinetic studies, vilazodone (20 mg) was administered to participants with mild, moderate, or severe hepatic impairment or individually matched healthy controls. Vilazodone and M17 (the major metabolite) concentrations in plasma were analyzed using validated liquid chromatography with tandem mass spectrometry. Forty-eight participants (8 each in mild, moderate, and severe hepatic impairment groups with matched healthy controls) were evaluated for pharmacokinetic analyses. All pharmacokinetic parameters in participants with mild and moderate hepatic impairment were similar to those in healthy controls. Mean Cmax and AUC0-∞ were approximately 29% and 17% lower in participants with severe hepatic impairment compared with healthy participants; values for Tmax, and t1/2 were similar between groups. Diarrhea was experienced by more participants with hepatic impairment than controls (10 vs. 5, respectively), and vomiting (4 participants) occurred only in participants with severe hepatic impairment; other adverse events were roughly equivalent between groups. Following a single, 20-mg oral dose of vilazodone, pharmacokinetics were similar in participants with mild, moderate, or severe hepatic impairment and healthy controls. No dose adjustment is needed for patients with major depressive disorder who have mild, moderate, or severe hepatic impairment.

Studies were carried out to characterize the secretion and the effects of calcitonin in the Buffalo rat. Mean basal concentrations of calcitonin and parathyroid hormone were significantly increased in serum of rats older than 6 months of age as compared with rats between 2 and 3 months of age. The mean concentration of calcium in serum was independent of age. In both age groups, serum calcitonin was increased by administration of calcium (1 mmol/kg body wt) or isoproterenol (100 microgram/kg body wt), was diminished by beta-adrenergic blockade with DL-propranolol (1 mg/kg body wt) and was not altered by either pentagastrin or glucagon (200 and 100 microgram/kg body wt respectively). The average weight of the thyroid glands was significantly greater in the old than in the young animals but the mean concentration of calcitonin in the thyroids was the same. Thyroparathyroidectomy produced a transient increase followed by a fall in mean serum calcium in the old rats. In contrast, a progressive decline in the mean concentration of calcium in serum was observed after thyroparathyroidectomy in the young rats. Treatment of old animals with reserpine (2.5 mg/kg body wt) markedly depleted noradrenaline in the thyroid, lowered calcitonin in serum and converted the pattern of response of serum calcium to thyroparathyroidectomy to that observed in young animals. The results provide evidence that hypercalcitonaemia occurs in aged Buffalo rats, as does hyperparathyroidism, and that the concentrations of calcitonin in blood are modulated by beta-adrenergic affectors. Glucagon and pentagastrin exhibit little if any effects on calcitonin secretion in this strain of rat regardless of age.