PII‐6

BACKGROUND Recognizing the growing significance of triglycerides (TG) and cardiovascular risk, the purpose of the study was to examine factors regulating TG response to fenofibric acid (FA)‐the active moiety of the PPAR‐α agonist fenofibrate. METHODS Subjects >=18 years with normal renal function, baseline fasting TG >=150 but < 1500mg/dL received fenofibrate 160mg every morning for 21 days after a 4 week washout of any lipid lowering drug(s) (LLD). Area under the concentration‐time curve (AUC 0–6 ) was used as a metric for post‐FA exposure from serum concentrations taken on day 21 at 0, 3.5, and 6 hours. A random effects effect model was used to investigate the effect of FA AUC 0–6 on log‐TG adjusting for sex, metabolic syndrome (MS) and previous LLD. RESULTS 204 subjects had a mean±sd(range) age of 55.8±13.2(18–81) years, pre‐FA TG of 245±120(150–1202) mg/dL, post‐FA TG of 142±66(41–419) mg/dL and AUC 0–6 of 71.8±33.1(5–202) mg/L*h. 107 were male, 120 with MS and 73 with previous LLD. Log‐TG levels post‐FA exposure decreased with increasing AUC 0–6 (p=0.015) in females regardless of previous LLD and males without previous LLD. There is a positive but non‐significant correlation (p=0.16) between log‐TG levels post‐FA exposure and AUC 0–6 in males with previous LLD. MS is positively correlated with log‐TG but does not have an interaction effect with AUC 0–6 . CONCLUSIONS An interaction between sex and previous LLD exposure exists for the correlation between FA AUC 0–6 and log‐TG response to fenofibrate. Clinical Pharmacology & Therapeutics (2005) 79 , P37–P37; doi: 10.1016/j.clpt.2005.12.131