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Background: Statins are the standard-of-care therapy for reducing low-density lipoprotein cholesterol (LDL-C) levels; however, combination with other lipid-modifying agents may be necessary to normalize lipid profiles in patients with mixed dyslipidemia who, in addition to high LDL-C, also have high triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C). Objective: This study aimed to evaluate the 1-year efficacy and safety of rosuvastatin in combination with fenofibric acid in a subgroup of patients treated for 12 weeks with rosuvastatin 10mg + fenofibric acid 135mg and subsequently treated for up to 52 weeks with rosuvastatin 20 mg+ fenofibric acid 135 mg. Methods: The efficacy and safety of combination therapy with rosuvastatin + fenofibric acid were demonstrated in a 12-week controlled study (NCT00300482) of patients with mixed dyslipidemia who were randomized to rosuvastatin 10, 20, or 40 mg, fenofibric acid 135 mg, or rosuvastatin 10 or 20mg + fenofibric acid 135 mg. All patients who completed the controlled study were eligible to enroll in a subsequent 52-week open-label extension study (NCT00300430) and received rosuvastatin 20mg + fenofibric acid 135 mg. The present post hoc analysis evaluated patients who were treated with rosuvastatin 10mg + fenofibric acid 135mg in the controlled study and received rosuvastatin 20mg + fenofibric acid 135mg in the open-label extension study. The study was carried out at investigative sites in the US (including Puerto Rico) and Canada. Patients included in the study were men and women ≥18 years of age with mixed dyslipidemia, defined as TG ≥150mg/dL, LDL-C ≥130mg/dL, and HDL-C <40/50mg/dL for men/women (at screening in the controlled trial). Efficacy variables included mean percentage changes in LDL-C, HDL-C, non-HDL-C, and apolipoprotein B (ApoB), andmedian percentage changes in TG and high-sensitivity C-reactive protein (hsCRP) from baseline (i.e. start of the open-label extension after 12 weeks of treatment with rosuvastatin 10mg + fenofibric acid 135 mg) to incremental time points up to 52 weeks in the extension study, and the proportion of patients achieving individual and combined goals for LDL-C and non-HDL-C. Adverse events (AEs) and clinical laboratory values were also assessed. Results: Of the 261 patients initially randomized to rosuvastatin 10mg + fenofibric acid 135 mg, 220 completed the controlled study and 187 continued treatment with rosuvastatin 20mg + fenofibric acid 135mg in the extension study. Increasing the rosuvastatin dose from 10mg to 20mg in combination with fenofibric acid 135mg for up to 52 weeks resulted in significant (p ≤ 0.005 for all comparisons) mean percentage changes from baseline in LDL-C (--9.5%), non-HDL-C (--6.0%), ApoB (--8.5%), and HDL-C (3.6%), while median TG levels remained largely unchanged (0.8%, p = 0.055) at the week 52 visit. Greater percentages of patients achieved their risk-stratified lipid goals at week 52 compared with baseline for LDL-C (89% vs 84%), non-HDL-C (50% vs 25%), and both LDL-C and non-HDL-C (50% vs 19%). Combination therapy was generally well tolerated. The incidence of muscle-, hepatic-, and renal-related AEs and laboratory values were within the expected range. Conclusion: This study demonstrates that 1-year therapy with rosuvastatin + fenofibric acid is well tolerated and that increasing the rosuvastatin dose from 10mg to 20 mg in the combination results in additional beneficial effects on key lipid parameters in patients with mixed dyslipidemia. [ABSTRACT FROM AUTHOR]

This study compared the gastrointestinal (GI) absorption characteristics and absolute bioavailability of fenofibric acid and fenofibrate (which is converted to fenofibric acid in vivo) in healthy volunteers. Treatments were delivered to the proximal small bowel, distal small bowel, and colon using a site-specific delivery system (Enterion capsule) and to the stomach by oral administration of equimolar doses. Serial blood samples were collected for 120 hours postdose and assayed for plasma fenofibric acid concentrations. The absolute bioavailability of each treatment was determined relative to 50 mg of fenofibric acid administered intravenously. Plasma exposure to fenofibric acid following fenofibric acid administration was approximately 1.5 times higher than that following fenofibrate administration for delivery to the proximal and distal small bowel and following oral administration, and it was approximately 5 times higher following colon delivery. The absolute bioavailability in the stomach, proximal small bowel, distal small bowel, and colon was approximately 81%, 88%, 84%, and 78%, respectively, for fenofibric acid and 69%, 73%, 66%, and 22%, respectively, for fenofibrate (P < .0001 and P = .033 for fenofibric acid vs fenofibrate in the colon and distal small bowel, respectively). In conclusion, fenofibric acid is well absorbed throughout the GI tract and has greater bioavailability than fenofibrate in all GI regions. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of fixed-dose combinations of rosuvastatin and fenofibric acid (rosuvastatin/fenofibric acid) compared with simvastatin in patients with high levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Background: Combination therapy with a statin and a fibrate is one of the treatment options to manage multiple lipid abnormalities in patients with hypercholesterolemia and elevated TGs. Methods: In this randomized, double-blind study, patients (n = 474) with LDL-C ≥160mg/dL and ≤240mg/dL and TG ≥150mg/dL and <400mg/dL were treated for 8 weeks with simvastatin 40 mg, rosuvastatin/fenofibric acid 5mg/135 mg, rosuvastatin/fenofibric acid 10 mg/135 mg, or rosuvastatin/ fenofibric acid 20 mg/135 mg. Primary and secondary variables were mean percent changes in LDL-C comparing rosuvastatin/fenofibric acid 20mg/135mg with simvastatin 40 mg and rosuvastatin/fenofibric acid 10 mg/135mg and rosuvastatin/fenofibric acid 5mg/135mg with simvastatin 40 mg, respectively. Additional efficacy variables included non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein (Apo) B, HDL-C, TG, and high-sensitivity C-reactive protein (hsCRP). Safety was evaluated based on data collected for adverse events (AEs), physical and electrocardiographic examinations, vital sign measurements, and clinical laboratory tests. Results: Significantly greater reductions in LDL-C levels from baseline values were observed with the combination of rosuvastatin/fenofibric acid 20mg/135mg (-47.2%, p< 0.001), rosuvastatin/fenofibric acid 10 mg/135mg (-46.0%, p< 0.001), and rosuvastatin/fenofibric acid 5mg/135mg (-38.9%, p= 0.007) than with simvastatin 40mg (-32.8%). Significant (p < 0.04 for all comparisons) improvements in non-HDL-C, ApoB, HDL-C, TG, and hsCRP levels were also observed with each of the rosuvastatin/fenofibric acid doses as compared with simvastatin 40 mg. Treatment-related AEs and discontinuations due to AEs were similar across groups. The incidence of serious AEs was 0% with simvastatin 40 mg, 3.4% with rosuvastatin/ fenofibric acid 5mg/135 mg, 0.8% with rosuvastatin/fenofibric acid 10mg/135 mg, and 2.5% with rosuvastatin/ fenofibric acid 20 mg/135 mg. No cases of rhabdomyolysis or drug-related myopathy were reported. Conclusion: In patients with high LDL-C and TGlevels, combination treatment with rosuvastatin/fenofibric acid was well tolerated, and each of the rosuvastatin/fenofibric acid doses produced greater reductions in LDL-C and improvements in other efficacy parameters, compared with simvastatin 40 mg. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) often have mixed dyslipidemia and high cardiovascular disease risk. Although statins reduce LDL-C, adding a fibrate may further improve lipid parameters. Objective: This multicenter, randomized study evaluated the short-term efficacy and safety profile of fenofibric acid (FA) + rosuvastatin (R) combination therapy for improving lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. The study also assessed estimated glomerular filtration rate after study drug washout. Methods: Patients received FA 45 mg + R (5 mg for 8 weeks, then 10 mg for 8 additional weeks) or R monotherapy (5 mg for 8 weeks, then 10 mg for 8 additional weeks), followed by an 8-week washout period. Primary and secondary end points were percent changes in triglycerides and HDL-C, respec-tively, from baseline to week 8. Results: FA 45 mg + R 5 mg, compared with R 5 mg, resulted in significant improvements in triglycer- ides (median % changes: week 8, -38.0% vs -22.4%, P < 0.001; week 16, -42.6% vs -29.7%, P < 0.001) and HDL-C (mean % changes: week 8, 16.9% vs 7.8%, P < 0.001; week 16, 17.3% vs 8.9%, P < 0.001). Adverse event rates were similar between groups (70.7% with FA + R vs 68.6% with R). Mean serum creatinine level at baseline was 1.36 mg/dL in the FA + R group and 1.38 mg/dL in the R group. The final treatment serum creatinine value, defined as the last nonmissing postbaseline value collected within 30 days after the last dose of study drug, was 1.52 mg/ dL with FA + R (vs 1.41 mg/dL with R; P < 0.001), which then decreased to 1.39 mg/dL after the 8-week washout (vs 1.42 mg/dL with R). Conclusions: The data suggest that, after 16 weeks of therapy, FA + R has an acceptable safety profile and improved TG and HDL-C efficacy versus R. FA + R combination therapy may thus further improve lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. ClinicalTrials.gov identifier: NCT00680017. [ABSTRACT FROM AUTHOR]

The combination of fibrate and statin therapies may be a treatment option for women with multiple lipid abnormalities. We, therefore, initiated the present safety and efficacy analysis to address the paucity of such data in women with mixed dyslipidemia. A total of 1,393 women with mixed dyslipidemia (low-density lipoprotein [LDL] cholesterol ≥130 mg/dl, triglycerides [TG] ≥150 mg/dl, high-density lipoprotein [HDL] cholesterol <50 mg/dl), who had enrolled in any 1 of 3 randomized clinical trials, were evaluated. The eligible women were randomized to receive fenofibric acid plus a low- or moderate-dose statin (combination treatment); or low-, moderate-, or high-dose statin monotherapy; or fenofibric acid monotherapy. With low-dose combination treatment, the baseline HDL cholesterol level increased 20% and TG decreased 46% compared to an 8% HDL cholesterol increase and 20% TG decrease with low-dose statins alone. With the moderate-dose combination, the baseline HDL cholesterol increased 21% and TG decreased 44% compared to an 8% HDL cholesterol increase and 26% TG decrease with moderate-dose statins alone. The reduction in baseline LDL cholesterol with low-dose and moderate-dose combinations (37% and 39%, respectively) was comparable to the reduction with corresponding-dose statins (36% and 43%, respectively). High-dose statins decreased the baseline LDL cholesterol 47%; however, the increase in HDL cholesterol (9%) and decrease in TG (25%) were similar to the changes observed with lower doses of statins. The safety profiles of the combinations were comparable to those of the component therapies. In conclusion, these data suggest that a combination of fenofibric acid and a statin could be considered safe and efficacious for treating women with mixed dyslipidemia. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To compare fenofibric acid (FA) + statin to respective monotherapies on the prevalence of metabolic syndrome and its diagnostic components in patients with mixed dyslipidemia. RESEARCH DESIGN AND METHODS-- Post hoc analysis of over 2,000 metabolic syndrome patients administered either FA + low- or moderate-dose statin; FA alone; or low-, moderate-, or high-dose statin alone. RESULTS -- FA + low- or moderate-dose statin combination therapy reduced the presence of metabolic syndrome (35.7 or 35.9%, respectively) more than low-, moderate-, or high-dose statin monotherapy (15.5, 16.6, or 13.8%, respectively), mostly due to improvements in triglycerides and HDL cholesterol levels. Mean glucose levels slightly decreased with FA monotherapy, slightly increased with statin monotherapy, and were essentially unchanged with FA + statin. FA with or without statin also reduced non-HDL cholesterol, apolipoprotein B, total cholesterol, VLDL cholesterol, and high-sensitivity C-reactive protein. CONCLUSIONS -- FA + statin in patients with mixed dyslipidemia reduces the prevalence of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Monotherapy with lipid-modifying medication is frequently insufficient to normalize lipid abnormalities in patients with mixed dyslipidemia and type 2 diabetes mellitus. Objective: To evaluate the efficacy and safety of fenofibric acid + statin combination therapy in this population. Study Design: A pooled, subgroup analysis of three randomized, controlled, double-blind, 12-week trials. Setting: Multiple clinical research facilities in the US and Canada. Patients: Patients with mixed dyslipidemia and type 2 diabetes (n = 586). Intervention: Fenofibric acid (Trilipix®) 135mg monotherapy; low-, moderate-, or high-dose statin monotherapy (rosuvastatin [Crestor®] 10, 20, or 40 mg; simvastatin [Zocor®] 20, 40, or 80 mg; or atorvastatin [Lipitor®] 20, 40, or 80 mg); or fenofibric acid + low- or moderate-dose statin. Main Outcome Measure: Mean percentage changes in lipid parameters, percentages of patients achieving optimal serum lipid/apolipoprotein levels, and incidence of adverse events. Results: Fenofibric acid + low-dose statin resulted in significantly (p < 0.001) greater mean percentage changes in high-density lipoprotein cholesterol (HDL-C) [16.8%] and triglycerides (-43.9%) than low-dose statin monotherapy (4.7% and -18.1%, respectively) and significantly (p < 0.001) greater reductions in lowdensity lipoprotein cholesterol (LDL-C) [-34.0%] than fenofibric acid monotherapy (-5.3%). Similarly, fenofibric acid + moderate-dose statin resulted in significantly (p < 0.011) greater mean percentage changes in HDL-C (16.3%) and triglycerides (-43.4%) than moderate-dose statin monotherapy (8.7% and -24.2%, respectively) and significantly (p < 0.001) greater reductions in LDL-C (-32.6%) than fenofibric acid monotherapy (-5.3%). Compared with low- or moderate-dose statin, fenofibric acid + low- or moderatedose statin resulted in over 5-fold higher percentages of patients achieving optimal levels of LDL-C, non- HDL-C, apolipoprotein B, HDL-C, and triglycerides simultaneously. Incidence of adverse events was generally similar among treatments. Conclusion: Fenofibric acid + statin combination therapy in patients with mixed dyslipidemia and type 2 diabetes was well tolerated and resulted in more comprehensive improvement in the lipid/apolipoprotein profile than either monotherapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Long-term (>1 year) safety and efficacy studies of combination lipid therapy are lacking. This year 2 study evaluated fenofibric acid 135mg in combination with moderate-dose statin (rosuvastatin 20 mg, simvastatin 40mg or atorvastatin 40mg) in patients with mixed dyslipidaemia. Methods: This was a phase 3, open-label, year 2 extension study in patients who had completed one of three double-blind, 12-week, controlled studies and the subsequent open-label, year 1 extension study. Patients in this study had mixed dyslipidaemia (high-density lipoprotein cholesterol [HDL-C] <40 mg/dL [<1.02 mmol/L] for men or <50 mg/dL [<1.28 mmol/L] for women, triglycerides [TG] ⩾150mg/dL [⩾1.69 mmol/L], and low-density lipoprotein cholesterol [LDL-C] ⩾130mg/dL [⩾3.37 mmol/L]) at the start of the controlled study, and had completed the year 1 extension study. Treatment was once-daily oral coadministration of fenofibric acid 135mg and moderatedose statin (rosuvastatin 20 mg, simvastatin 40mg or atorvastatin 40 mg), and was identical to the treatment received in the year 1 study. The year 2 population safety data were summarized for the entire duration of fenofibric acid + statin therapy. Efficacy data were summarized by combination therapy group, as well as pooled across combination therapies, and summarized across the controlled and open-label studies. Results: Of the 310 patients enrolled into the year 2 study, 287 (93%) completed therapy. The mean cumulative exposure to combination therapy was 743 days across the studies. Adverse event rates were similar for all three combination therapy groups. No deaths or treatment-related serious adverse events occurred. The incidence of discontinuation due to adverse events was 2.9% overall. Rhabdomyolysis was not reported in any group. Overall, fenofibric acid + moderate-dose statin for ⩾2 years resulted in sustained improvements in HDL-C (+17.4%), TG (-46.4%) and LDL-C (-40.4%). Conclusions: This long-term study demonstrated that fenofibric acid + moderate-dose statin was generally well tolerated with no new or unexpected safety concerns, and resulted in comprehensive and sustained lipid improvements in patients with mixed dyslipidaemia. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate a new formulation of fenofibric acid (ABT-335) co-administered with 2 doses of rosuvastatin in patients with mixed dyslipidemia. Methods: In a phase 3, multicenter, randomized, double-blind, active-controlled study, a total of 1445 patients with LDL-C≥130mg/dL, TG≥150mg/dL, and HDL-C<40mg/dL (<50mg/dL for women) were randomized to either ABT-335 (135mg), rosuvastatin (10, 20, or 40mg), or ABT-335+rosuvastatin 10 or 20mg, and treated for 12 weeks. The primary efficacy comparisons were mean percent change in HDL-C and TG (ABT-335+rosuvastatin vs. corresponding dose of rosuvastatin), and LDL-C (ABT-335+rosuvastatin vs. ABT-335). Results: Combination therapy with ABT-335+rosuvastatin 10mg resulted in significantly (p <0.001) greater improvements in HDL-C (20.3% vs. 8.5%) and TG (−47.1% vs. −24.4%) compared to rosuvastatin 10mg; and LDL-C (−37.2% vs. −6.5%) compared to ABT-335. Similarly, significantly (p <0.001) greater improvements were observed with ABT-335+rosuvastatin 20mg in HDL-C (19.0% vs. 10.3%) and TG (−42.9% vs. −25.6%) compared to rosuvastatin 20mg; and LDL-C (−38.8% vs. −6.5%) compared to ABT-335 monotherapy. Greater improvements in multiple secondary endpoints were noted with combination therapy compared to prespecified monotherapies. Both combination therapy doses were generally well tolerated, with a safety profile consistent with ABT-335 and rosuvastatin monotherapies. No rhabdomyolysis or unexpected hepatic, renal, or muscle safety signals were identified. Conclusion: In patients with mixed dyslipidemia, combination therapy with ABT-335+rosuvastatin resulted in more effective control of multiple lipid parameters than either monotherapy alone, with a safety profile similar to both monotherapies. This combination may be an appropriate therapeutic option to treat mixed dyslipidemia. [Copyright &y& Elsevier]

In patients with mixed dyslipidemia characterized by increased triglycerides (TG), decreased high-density lipoprotein (HDL) cholesterol, and increased low-density lipoprotein (LDL) cholesterol, monotherapy with lipid-altering drugs often fails to achieve all lipid targets. This multicenter, double-blind, active-controlled study evaluated ABT-335 (fenofibric acid) in combination with 2 doses of atorvastatin in patients with mixed dyslipidemia. A total of 613 patients with LDL cholesterol ≥130 mg/dl, TG ≥150 mg/dl, and HDL cholesterol <40 mg/dl for men and <50 mg/dl for women were randomly assigned to ABT-335 (135 mg), atorvastatin (20, 40, or 80 mg), or combination therapy (ABT-335 + atorvastatin 20 or 40 mg) and treated for 12 weeks. Combination therapy with ABT-335 + atorvastatin 20 mg resulted in significantly greater improvements in TG (−45.6% vs −16.5%) and HDL cholesterol (14.0% vs 6.3%) compared with atorvastatin 20 mg and LDL cholesterol (−33.7% vs −3.4%) compared with ABT-335. Similarly, significantly greater improvements were observed with ABT-335 + atorvastatin 40 mg in TG (−42.1% vs −23.2%) and HDL cholesterol (12.6% vs 5.3%) compared with atorvastatin 40 mg and LDL cholesterol (−35.4% vs −3.4%) compared with ABT-335 monotherapy. Combination therapy also improved multiple secondary variables. Combination therapy was generally well tolerated with a safety profile consistent with those of ABT-335 and atorvastatin monotherapies. No rhabdomyolysis was reported. In conclusion, ABT-335 + atorvastatin combination therapy resulted in more effective control of multiple lipid parameters than either monotherapy and may be an appropriate therapy for patients with mixed dyslipidemia. [Copyright &y& Elsevier]

ABT-335 is the choline salt of fenofibric acid under clinical development as a combination therapy with rosuvastatin for the management of dyslipidemia. ABT-335 and rosuvastatin have different mechanisms of actions and exert complementary pharmacodynamic effects on lipids. The current study assessed the pharmacokinetic interaction between the 2 drugs following a multiple-dose, open-label, 3-period, randomized, crossover design. Eighteen healthy men and women received 40 mg rosuvastatin alone, 135 mg ABT-335 alone, and the 2 drugs in combination once daily for 10 days. Blood samples were collected prior to dosing on multiple days and up to 120 hours after day 10 dosing for the measurements of fenofibric acid and rosuvastatin plasma concentrations. Coadministering 40 mg rosuvastatin had no significant effect on the steady-state C[submax], C[submin], or AUC[sub24] of fenofibric acid (P > .05). Coadministering ABT-335 had no significant effect on the steady-state C[submax] or AUC[sub24] of rosuvastatin (P > .05) but increased C[submax] by 20% (90% confidence interval: 12%-28%). All 3 regimens were generally well tolerated with no clinically significant changes in clinical laboratory values, vital signs, or electrocardiograms during the study. Results from this study demonstrate no clinically significant pharmacokinetic interaction between ABT-335 at the full clinical dose and rosuvastatin at the highest approved dose. [ABSTRACT FROM AUTHOR]

BACKGROUND: and objective: Atherogenic lipid parameters in patients with mixed dyslipidaemia have been demonstrated to increase atherosclerotic coronary heart disease (CHD) risk. Clinical studies have shown that HMG-CoA reductase inhibitor (statin) and fibric acid derivative (fibrate) combination therapy is effective at improving multiple lipid abnormalities in different patient populations at increased risk of CHD. However, inconsistencies with respect to trial designs and safety issues have limited the clinical use of this combination therapy. A comprehensive, controlled clinical trial programme was thus designed to evaluate three separate statins in combination with ABT-335, a new formulation of fenofibric acid. METHODS: Three separate 22-week, phase III, double-blind, active-controlled trials will evaluate combination therapy with ABT-335 135 mg/day and either rosuvastatin (10 mg/day and 20 mg/day), atorvastatin (20 mg/day and 40 mg/day) or simvastatin (20 mg/day and 40 mg/day) in comparison to either ABT-335 or the corresponding statin monotherapy. An approximate total of 2400 patients with elevated triglycerides (TG) [≥150 mg/dL], reduced high-density lipoprotein cholesterol (HDL-C) [<40 mg/dL for men and <50 mg/dL for women], and elevated low-density lipoprotein cholesterol (LDL-C) [≥130 mg/dL] will be randomized to one of six intervention arms per trial (two combination therapy and four monotherapy groups). The pre-specified primary efficacy endpoint is a composite of the mean percent changes in HDL-C and TG (comparing each combination therapy with the corresponding statin monotherapy dose) and LDL-C (comparing each combination therapy with ABT-335 monotherapy). Secondary endpoints include mean percent changes in non-HDL-C, very LDL-C, total cholesterol, apolipoprotein B and high sensitivity C-reactive protein levels. At study end, patients may enrol in a 12-month open-label extension study that will evaluate the long-term efficacy and safety of combination therapy. CONCLUSION: This is the largest phase III randomized, controlled clinical programme to date evaluating the efficacy and safety of the combined use of a new formulation of fenofibric acid (ABT-335) with three commonly prescribed statins in patients with mixed dyslipidaemia. [ABSTRACT FROM AUTHOR]

Abstract: Objective:: This study was conducted to evaluatethe potential for pharmacokinetic interaction between fenofibrate and ezetimibe in healthy subjects. Methods:: This was a Phase I, open-label, multiple-dose,3-period crossover study conducted in healthy adult men and women. Subjects received fenofibrate 145 mg alone, fenofibrate 145 mg with ezetimibe 10 mg, and ezetimibe 10 mg alone for 10 consecutive days, in an order determined by computerized randomization schedule. Blood samples were collected for up to 24 hours after dosing on study day 1 and up to 120 hours after dosing on study day 10 for determination of plasma concentrations of fenofibric acid, unconjugated (free) ezetimibe, and total (conjugated and unconjugated) ezetimibe using validated high-performance liquid chromatography methods with mass-spectrometric detection. Ezetimibe glucuronide concentrations were estimated by subtracting free ezetimibe concentrations from total ezetimibe concentrations. Results:: Eighteen healthy adults (12 men, 6 women; 17 white, 1 black) were enrolled in the study. Their mean age was 43.4 years (range, 27–55 years), their mean weight 78.7 kg (range, 60–98 kg), and their mean height 174.9 cm (range, 156–194 cm). Coadministration of multiple doses of fenofibrate and ezetimibe produced no statistically significant effect on the pharmacokinetics of fenofibric acid but significantly increased exposures to total ezetimibe and ezetimibe glucuronide (P < 0.05). Using point estimates, co-administration of fenofibrate and ezetimibe increased AUC central values for total ezetimibe and ezetimibe glucuronide by 43% (90% CI, 29–59) and 49% (90% CI, 34–65), respectively. Conclusion:: In these healthy volunteers, coadministrationof multiple doses of fenofibrate and ezetimibe had no statistically significant effect on the pharmacokinetics of fenofibric acid but was associated with a significant increase in exposure to total ezetimibe and its metabolite ezetimibe glucuronide. [Copyright &y& Elsevier]