Evaluation of the Pharmacokinetic Drug–Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers

Dyslipidemia is a major risk factor for development of atherosclerosis and cardiovascular disease (CVD). Effective lipid-lowering therapies has led to CVD risk reduction. This study evaluated the possible pharmacokinetic interactions between fenofibrate, a peroxisome proliferators-activated receptors α agonist, and pitavastatin, a 3-hydoxy-3-methylglutaryl-coenzyme A reductase inhibitor, in healthy Korean subjects. The study design was an open-label, randomized, multiple-dose, three-period, and six-sequence crossover study with a 10-day washout in 24 healthy volunteers. It had three treatments: 160 mg of micronized fenofibrate once daily for 5 days; 2 mg of pitavastatin once daily for 5 days; and 160 mg of micronized fenofibrate with 2 mg of pitavastatin for 5 days. Serial blood samples were collected at scheduled intervals for up to 48 h after the last dose in each period to determine the steady-state pharmacokinetics of both drugs. Plasma concentrations of fenofibric acid and pitavastatin were measured using a validated high-performance liquid chromatography with the tandem mass spectrometry method. A total of 24 subjects completed the study. Pitavastatin, when co-administered with micronized fenofibrate, had no effect on the Cmax,ss and AUCτ,ss of fenofibric acid. The Cmax,ss and AUCτ,ss of pitavastatin were increased by 36% and 12%, respectively, when co-administered with fenofibrate. Combined treatment with pitavastatin and micronized fenofibrate was generally well tolerated without serious adverse events. Our results demonstrated no clinically significant pharmacokinetic interactions between micronized fenofibrate and pitavastatin when 160 mg of micronized fenofibrate and 2 mg of pitavastatin are co-administered. The treatments were well tolerated during the study, with no serious adverse events.

Experience of the treatment of diabetic macular edema in patients with diabetes mellitus type II on the background of correction of lipid metabolism

Problem. According to current observations, the increase in free cholesterol, low-density lipoprotein and triglyceride levels associated with the risk of diabetic macular edema (DME). Purpose. To study the effectiveness of pharmacological micronized fenofibrate, 145 mg in the complex treatment of patients with type II diabetes with diabetic macular edema. Material and methods. Two groups of patients with diabetes type II and DME were investigated. In the first group, patients received the fenofibrate, 145 mg during 8 months and onetime intraocular injection of aflіbersept; in the second one – only intraocular injection of aflіbersept. Assessment of the retina produced in all terms by visual acuity and retinal thickness of macular area with optical coherence tomography Stratus-3000 with control of the lipid parameters in blood serum. Results. In 8 months in group I, who obtained the drug fenofibrate, 145 mg, marked and more positive trend in ophthalmic and biochemical parameters and improve lipid profile were revealed. Conclusion. The paper presents the results of the comparative analysis to determine the effectiveness of micronized fenofibrate (Traykor®145 mg) in complex microsurgical treatment of DME with the control of the dynamics of changes in lipid parameters of blood serum was done.

Carbohydrate-lipid profile and use of metformin with micronized fenofibrate in reducing metabolic consequences of craniopharyngioma treatment in children: single institution experience

To evaluate auxology and metabolic disturbances in children with craniopharyngioma, and to present observational results of treatment of metabolic sequels with metformin and micronized fenofibrate.The studied group comprised 22 children [median age at diagnosis 10.5 (0.17–16.75) years; median follow-up 5.1 years]. Assessment included height standard deviations (SDS), body mass index (BMI) SDS, concentrations of lipids, glucose and insulin (fasting or oral glucose tolerance test) and homeostatic model assessment of insulin resistance (HOMA-IR) index. Ten adolescents with hyperinsulinemia and dyslipidemia received therapy with metformin (500–1500 mg/daily) and micronized fenofibrate (160 mg/daily).At diagnosis, median hSDS was –1.66 (range: –4.08; +0.1). Nine (40.9%) children were growth hormone-treated. There was gradual increase of BMI SDS, 18 (81.8%) patients being overweight at the final assessment. Dyslipidaemia was found in 19 patients (86.4%), hyperinsulinaemia in 11 patients (50%) and elevated HOMA-IR in 15 patients (68.2%). Decrease of triglycerides [median 263.5 (171–362) mg/dL vs. 154 (102–183) mg/dL] and HOMA-IR [8.64 (5.08–12.65) vs. 4.68 (0.7–7.9)] was significant in the group treated with metformin and fenofibrate for 6 months.Significant auxologic changes and metabolic abnormalities were found in children treated for craniopharyngioma. The use of metformin and fenofibrate seemed to attenuate these disturbances in a short-term observation.

Fenofibrate in Primary Biliary Cirrhosis: A Pilot Study

Background: Most patients with primary biliary cirrhosis (PBC) are treated with ursodeoxycholic acid (UDCA); however, some do not respond fully. PBC is also associated with dyslipidemia, but a link with vascular risk has not been confirmed. Methods and Results: In this study we compared UDCA monotherapy with fenofibrate plus UDCA in PBC patients with incomplete biochemical response to UDCA monotherapy for ≥ 8 months. Ten patients (57.2±13.3 years old) with PBC and persistent elevations of liver enzymes after treatment with UDCA (600 mg/day) were randomized to continue UDCA (4 patients) or to receive micronized fenofibrate (200 mg/day) plus UDCA (6 patients) for 8 weeks. Significant reductions in total cholesterol, triglycerides and non-high density lipoprotein cholesterol were observed in the combination treatment group. The serum activities of alkaline phosphatase, gamma-glutamyl transpeptidase and alanine aminotranferase also decreased in this group compared with baseline (-32.6%; p=0.012, -44%; p=0.031 and -16.9%; p=0.029, respectively). In contrast, no significant alterations in liver enzymes or lipid profile were observed in patients who continued UDCA monotherapy. The changes in the lipid and enzyme variables differed significantly (p<0.03) between the 2 groups. Fenofibrate was well tolerated. Conclusions: The administration of fenofibrate plus UDCA seems to be safe and may improve lipid and liver indices in patients with PBC who do not respond fully to UDCA monotherapy. Whether the improved lipid profile translates into a decreased risk of vascular events remains to be established.

Moxonidin in combined therapy of metabolic syndrome

The paper presents the results of 24-weeks follow-up and treatment patients with metabolic syndrome. It shows antihypertensive effect of imidazoline-receptor agonist moxonidine and hypolipidemic effect of micronized fenofibrate in patients with metabolic syndrome. The combination demonstrate synergic action on carbohydrate and uric acid metabolism. Thus, it can significantly decrease the level of cardio-vascular risk (SCORE) in patients with metabolic syndrome.