Prolonged retention of doubly labeled phosphatidylcholine in human plasma and erythrocytes after oral administration.
The plasma kinetics of a preparation of dilinoleoyl phosphatidylcholine (DLPC) specifically labeled with 3H in the choline moiety and with 14C in the 2-fatty acid (FA) were evaluated in six healthy volunteers after oral administration. Retention of both isotopes in plasma exceeded expectations, with a half-life in the elimination phase of 172.2 h for 3H and 69.7 h for 14C. Up to 60 d after administration, there were still significant levels of radioactivity present in plasma. The relative stability of the [14C]FA label was demonstrated by the retention for more than 12 h of an isotope ratio close to that of the compound administered. The 14C label of DLPC remained in position-2, as assessed by cleavage of plasma phospholipids with phospholipase A2. The [3H]choline label showed an early incorporation into high density lipoproteins and subsequently into low density lipoproteins (LDL); conversely, the 14C radioactivity was rapidly incorporated into triacylglycerols that were mainly associated with very low density lipoproteins. Radioactivity measurements revealed that both isotopes remained the longest time in LDL. In red blood cell (RBC) lipids, [3H]choline radioactivity accumulated over time, with a plateau after 48 h, whereas FA radioactivity accumulated more rapidly and was followed by a progressive decay. Analysis of the isotope ratio in these cells suggested an early incorporation of lyso products followed by rapid transfer of FA from plasma. The RBC maintained considerable radioactivity for a prolonged time, thus acting as a possible reservoir for the DLPC administered.(ABSTRACT TRUNCATED AT 250 WORDS)
Galli
C
C
Institute of Pharmacological Sciences, School of Sciences, University of Milan, Italy.
Sirtori
C R
CR
Mosconi
C
C
Medini
L
L
Gianfranceschi
G
G
Vaccarino
V
V
Scolastico
C
C
D000284:Administration, Oral; D000328:Adult; D002794:Choline / Q000097:blood / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008042:Linolenic Acids / Q000097:blood / Q000493:pharmacokinetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D010713:Phosphatidylcholines / Q000493:pharmacokinetics*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010949:Plasma / Q000378:metabolism*
D008042:Linolenic Acids; D008055:Lipids; D008074:Lipoproteins; D010713:Phosphatidylcholines; C002448:1,2-linoleoylphosphatidylcholine; D010741:Phospholipases A; D054467:Phospholipases A2; D002794:Choline