The metabolism of the xenobiotic triacylglycerols, rac-1- and sn-2-(3-phenoxybenzoyl)-dipalmitoylglycerol, following intravenous administration to the rat

The metabolism of 3-phenoxybenzoic acid (3PBA) in the form of triacylglycer ol conjugates was compared with that of non-esterified 3PBA. Three radiolab eled triacylglycerols (rac-1-(3-phenoxy-[ring-C-14]- benzoyl)-2,3-dipalmito ylglycerol (1(3PBA)DPG), sn-2-(3-phenoxy-[ring-C-14]benzoyl)-1,3-dipalmitoy lglycerol (2(3PBA)DPG) and the "natural" tri-[1-C-14]oleoylglycerol) were i ncorporated into rat VLDL. Nonesterified 3PBA was prepared in rat serum alb umin solution. Each preparation was administered i.v. to rats and serial bl ood samples were taken during the subsequent 6 hr. Urine and faeces were co llected and tissue residues determined at 6 hr and 48 hr after administrati on. Biphasic elimination of 3PBA was observed with half-lives of 18 min and 2 hr. The triacylglycerols showed a rapid first phase and a longer second phase half-life: trioleoylglycerol 26 hr, I(3PBA)DPG 7.6 hr and 2(3PBA)DPG 17.3 hr. The majority (63-76%) of 3PBA (whether esterified or not) was elim inated within 24 hr in urine, which contained similar profiles of metabolit es. The triacylglycerols gave rise to higher tissue residues than did non-e sterified 3PBA, particularly in adipose tissue which alone was not signific antly depleted of radioactivity between 6 and 48 hr. The results accord wit h the rapid association of the VLDL-(3PBA)DPG complexes with lipoprotein li pase of the capillary epithelium, followed by hydrolysis to 3PBA, metabolis m and elimination but with a proportion being redistributed into adipose ti ssue, re-esterified and then eliminated relatively slowly. BIOCHEM PHARMACO L 56;12:1599-1606, 1998. (C) 1998 Elsevier Science Inc.