Journal of Pharmacobio-Dynamics
Online ISSN : 1881-1353
Print ISSN : 0386-846X
ISSN-L : 0386-846X
Characteristics of 1, 3-Bis-(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy) propane Dihydrochloride (N-556), a Prodrug for the Oral Delivery of Disodium Cromoglycate, in Absorption and Excretion in Rats and Rabbits
キーワード: first-pass effect
ジャーナル フリー

1992 年 15 巻 12 号 p. 681-686


The absorption and excretion of 1, 3-bis-(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy) propane dihydrochloride (N-556), which is a prodrug for the oral delivery of disodium cromoglycate (DSCG), were studied in rats and rabbits. In both animal species, the plasma concentration of DSCG after oral administration of N-556 peaked within 1.0 h, and thereafter declined with a half-life of about 1.2 h in rats and rabbits. The area under the plasma DSCG level versus time curve (AUC) increased in proportion to the dose of N-556 in both animals. The bioavailability of N-556 as calculated from AUC was about 6% in rats and 40% in rabbits, whereas that of DSCG was only 0.1% in rats and 2.5% in rabbits. About 2% and 15% of the dose were respectively excreted as DSCG in the urine and bile after the oral administration of N-556 in rats. The ratio of biliary excretion to urinary excretion (B/U) after the oral administration of N-556 was about twice that after the intravenous injection of DSCG. In rabbits, the urinary and biliary excretions of DSCG after oral administration of N-556 were about 25% and 5%, respectively. The B/U ratio after the oral administration of N-556 in rabbits was similar to that after intravenous administration of DSCG. The difference in the systemic bioavailability of N-556 between rats and rabbits thus appears to be due to a first-pass effect, in addition to a difference in the absorption rate.

© The Pharmaceutical Society of Japan
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