A population PK model of EPA and DHA after intake in phospholipid as well as in triglyceride form.
Nils Hoem (1), Kristin C. Carlsson
(1) Aker BioMarine Oslo, Norway
Objectives: The objective of this work was to establish a population (pharmaco) kinetic model of the plasma and phospholipid fractions of the two omega-3 fatty acids eicosapenatenoic acid (EPA) and docosehexaenoic acid (DHA), after administration in both phospholipid and triglyceride form.
Methods: Concentration time profiles of the two essential fatty acids EPA and DHA were assessed in 36 human volunteers. The experiment was conducted under strict control of food intake during a 12 day cross over study. Subject’s acceptance of informed consent, planning, conduct and reporting of the study were performed in accordance with current ICH guidelines in a phase 1 clinic. Dense sampling of plasma was made for each subject during four 72 hour dosing intervals. Freshly frozen plasma samples were assayed for omega-3 fatty acids by a standard a GC-FID method.
Results: A population PK method was elaborated describing the endogenous as well as the exogenous variation in plasma as well as plasma phospholipids levels of EPA and DHA. The model incorporated dual input from both phospholipids and triglyceride sources and incorporated loss from and interaction between total plasma and the plasma phospholipids fraction. The modelling was performed in NONMEM v. 7
Conclusions: A population PK model was established that describe exogenous and endogenous loss and interchange of the omega 3 fatty acids EPA and DHA from and between plasma and plasma phospholipids.