TY - JOUR
T1 - Relative Bioavailability of an Emulsion Formulation for Omega-3-Acid Ethyl Esters Compared to the Commercially Available Formulation
T2 - A Randomized, Parallel-Group, Single-Dose Study Followed by Repeat Dosing in Healthy Volunteers
AU - Hussey, Elizabeth K.
AU - Portelli, Samm
AU - Fossler, Michael J.
AU - Gao, Feng
AU - Harris, William S.
AU - Blum, Robert A.
AU - Lates, Christian D.
AU - Gould, Elizabeth
AU - Abu-Baker, Omar
AU - Johnson, Susan
AU - Reddy, Karunakar K.
PY - 2012/1
Y1 - 2012/1
N2 - LOVAZA (omega-3-acid ethyl esters; eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]), with diet, lowers very high triglycerides (≥500 mg/dL) in adults. This study evaluated whether an emulsion formulation (LEM) increases the bioavailability of EPA/DHA compared to the reference formulation (RF) in healthy volunteers. Following relative bioavailability assessment, LEM, RF, and placebo were dosed for 2 weeks. Exposure measurements included plasma-free and total fatty acid (EPA/DHA) concentrations and phospholipid and red blood cell (RBC) incorporation. Following single doses, the dose-normalized EPA plasma-corrected AUCs were 14-fold (total) and 12-fold (free) higher and DHA plasma-corrected AUCs were 10-fold (total) and 13-fold (free) higher for LEM compared to RF. EPA and DHA incorporation into phospholipids increased for all active treatments; the increase was dose dependent for EPA. An 8-fold increase over baseline was observed in EPA incorporation for LEM (4-capsule dose) compared to a 4-fold increase for RF 4 g. DHA incorporation increased to a lesser degree, and RBC incorporation also increased. Pharmacodynamic evaluations revealed slight decreases (-8% to -25%) in the mean fasting triglyceride concentrations in all groups, including placebo, compared to baseline. Following a high-fat meal, no consistent treatment-related effect on the triglyceride profiles was observed. Study treatments were safe and tolerated. In conclusion, LEM improves the oral bioavailability of EPA and DHA.
AB - LOVAZA (omega-3-acid ethyl esters; eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]), with diet, lowers very high triglycerides (≥500 mg/dL) in adults. This study evaluated whether an emulsion formulation (LEM) increases the bioavailability of EPA/DHA compared to the reference formulation (RF) in healthy volunteers. Following relative bioavailability assessment, LEM, RF, and placebo were dosed for 2 weeks. Exposure measurements included plasma-free and total fatty acid (EPA/DHA) concentrations and phospholipid and red blood cell (RBC) incorporation. Following single doses, the dose-normalized EPA plasma-corrected AUCs were 14-fold (total) and 12-fold (free) higher and DHA plasma-corrected AUCs were 10-fold (total) and 13-fold (free) higher for LEM compared to RF. EPA and DHA incorporation into phospholipids increased for all active treatments; the increase was dose dependent for EPA. An 8-fold increase over baseline was observed in EPA incorporation for LEM (4-capsule dose) compared to a 4-fold increase for RF 4 g. DHA incorporation increased to a lesser degree, and RBC incorporation also increased. Pharmacodynamic evaluations revealed slight decreases (-8% to -25%) in the mean fasting triglyceride concentrations in all groups, including placebo, compared to baseline. Following a high-fat meal, no consistent treatment-related effect on the triglyceride profiles was observed. Study treatments were safe and tolerated. In conclusion, LEM improves the oral bioavailability of EPA and DHA.
KW - DHA
KW - EPA
KW - emulsions
KW - omega-3-acid ethyl esters
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=84891988089&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891988089&partnerID=8YFLogxK
U2 - 10.1177/2160763X11431107
DO - 10.1177/2160763X11431107
M3 - Article
AN - SCOPUS:84891988089
SN - 2160-763X
VL - 1
SP - 14
EP - 23
JO - Clinical Pharmacology in Drug Development
JF - Clinical Pharmacology in Drug Development
IS - 1
ER -