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Absorption and metabolism of the absorption enhancer didecanoylphosphatidylcholine in rabbit nasal epithelium in vivo.

Drug metabolism and disposition: the biological fate of chemicals (1997-10-06)
C Vermehren, P B Johansen, H S Hansen
ABSTRACT

The absorption enhancer, didecanoylphosphatidylcholine (DDPC), improves the nasal absorption of human growth hormone in rabbits. We elucidated the uptake and the metabolism of 1,2-di[1-14C]decanoyl-L-3-phosphatidylcholine and 1,2-didecanoyl-L-3-phosphatidyl[N-methyl-3H]choline in rabbit nasal mucosa in vivo. One minute after nasal application of DDPC, 4.4-7.5% of the applied dose was found absorbed into the mucosa. The retained radioactivity left the tissue in <2 hr. The lipophilic tissue extract revealed that, at t = 1 min, only 1.1-1.4% of the applied dose was found as intact DDPC in the nasal mucosa. The other labeled compounds were decanoic acid, DDPC reacylated with endogenous fatty acids, a neutral lipid, and very small amounts of lyso-DDPC and phosphatidylethanolamine. The water-soluble metabolites revealed formation of phosphorylcholine, glycerophosphorylcholine, cytidinediphosphatecholine, and a slight amount of choline. The detection of these metabolites suggests that DDPC was rapidly cleared from the nasal mucosa, partly by degradation by phospholipases. In addition, data illustrated reutilization of DDPC metabolites in the formation of cytidinediphosphatecholine and phosphatidylethanolamine, together with DDPC being reacylated with endogenous fatty acids. The rapid formation of decanoic acid raises the possibility that this acid may contribute significantly to the drug-enhancing properties of DDPC.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
1,2-Didecanoyl-sn-glycero-3-phosphocholine, ≥99% (TLC)

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