Gastric ulceration and the concentration of salicylate in plasma in rats after administration of 14C-labelled aspirin and its synthetic triglyceride, 1,3-dipalmitoyl-2(2′-acetoxy-[14C]carboxylbenzoyl) glycerol

Abstract

Triglycerides containing aspirin in place of one or more fatty acid residues of the molecule have been synthesized. Metabolism of the compound with the labelled (14C) drug residue introduced specifically into the 2‐position of the triglyceride is reported. Plasma salicylate concentrations with this synthetic glyceride were determined and compared with those obtained with commercially available aspirin labelled with the 14C‐isotope. Both compounds gave a therapeutic concentration of salicylate in the plasma after ingestion. The 1,3‐di‐fatty acyl‐2‐aspirin glyceride was absorbed through the intestine as 2‐aspirin monoglyceride, some 20% of which was transported through the thoracic‐duct chyle and about 30% through the portal system. Whereas pronounced ulceration of the rat stomach occurred with free aspirin, the above fatty acyl glyceride of aspirin produced no ulceration.

Bio-distribution in rats of some salicylates with low gastric ulcerogenicity

“…While benorylate is certainly less ulcerogenic than ASA [2,24], much larger quantities are required to achieve therapeutic levels and efficacy comparable to ASA [25]. Of the other esters, the triglyceride is very slowly absorbed compared with ASA [26]. This may also be a problem with other esters, e.g.…”

“…[23]). Several ester pro-drugs of ASA have been developed in recent years [24][25][26][27][28][29][30][31]. Among these the paracetamol ester (benorylate) has been the most widely adopted in clinical use.…”

Enzymatic Synthesis of Structured Lipids

“…This concept might be related to drug delivery technology, including so-called "DG prodrugs", which are 1,3-diacyl-sn-glycerols with various drugs attached to glycerol's sn-2 position [15][16][17][18]. Figure 1 shows a typical synthetic scheme for MLM-type STGs.…”

Anti-inflammatory/anti-pyretic salicylic acid esters with low gastric ulcerogenic activity

“…For example, the low rate of hydrolysis of benorylate (the paracetamol ester of aspirin) and a new triglyceride of aspirin (see Ref. [21]) in vivo may account for the reduced effectiveness of these drugs when compared on a molar basis with that of aspirin, even though their ulcerogenic activity is somewhat lower compared with that of aspirin [1, 10, 20 21]. Aspirin methyl ester may, Table 3 Anti-inflammatory effects of aspirin esters in rats with established adjuvant-arthritis.…”