Studies on Intestinal Lymphatic Absorption of Drugs. II. Glyceride Prodrugs for Improving Lymphatic Absorption of Naproxen and Nicotinic Acid

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A series of α-and β-monoglycerides and triglyceride derivatives of naproxen or nicotinic acid were synthesized and investigated in order to elucidate the molecular form of the derivative with properties that enhanced lymphatic absorption. The lymphatic absorption rate was increased by adjusting the length of an n-alkyl chain introduced between the α-or β-position of glycerol and the drug residue. The α-and β-monoglyceride derivatives (containing an n-alkyl chain) were approximately equal in lymphatic absorption rates, but differed markedly in the concentration of the di-and triglyceride analogues in the lymph lipids. The lymphatic absorption of triglyceride derivatives, drugs combined directly with β-position of glycerol, was low in comparison with the monoglyceride derivatives. Compared with nicotinic acid, the α-monoglyceride derivative (n-alkyl chain length, C_<n=20>) of nicotinic acid provided a higher AUC_<0-8h> value of free nicotinic acid and maintained a lower level of free fatty acids in blood.
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