Comparison of the gastrointestinal absorption and bioavailability of fenofibrate and fenofibric acid in humans.
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.
Zhu
Tong
T
100 Abbott Park Road, Dept R4PK, Bldg AP13A-3, Abbott Park, IL 60064-6104, USA. tong.zhu@abbott.com
Ansquer
Jean-Claude
JC
Kelly
Maureen T
MT
Sleep
Darryl J
DJ
Pradhan
Rajendra S
RS
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D016503:Drug Delivery Systems; D011345:Fenofibrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D055815:Young Adult
D000960:Hypolipidemic Agents; C006012:fenofibric acid; D011345:Fenofibrate