Pharmacokinetics and disposition of the novel dopamine agonist Z-7760 in rat after intravenous and oral administration

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
M BollardC Semeraro

Abstract

1. Z-7760 (S(-)-N-[N-2-phenylethyl)-6-hexylamino]-N-propyl-5,6-dihydroxy-1,2,3,4-tetrahydro-2-naphthylamine dihydrobromide) is a potent dopamine D-1 and D-2 agonist synthesized during a search for agents to treat heart failure. Reported is the fate of the drug in rat. 2. 3H-Z-7760 was administered p.o. and i.v. to male Sprague-Dawley rats (0.4 mg and 400 microCi/kg in 0.1% ascorbic acid) and venous blood samples collected at intervals up to 48 h. Comparison of the AUC for total 3H showed that 37% of an oral dose of Z-7760 was absorbed. The percentage plasma 3H present as the parent compound fell from 82% 30 min after i.v. dosing to 12% after 24 h. After oral dosing, the fraction of plasma 3H present as unchanged Z-7760 was < 5% and this was essentially unaltered throughout the study. The long terminal elimination phase evident from 6 h was notable after both routes of administration. 3. The bile duct-cannulated rat was given 3H-Z-7760 p.o. (0.4 mg and 40 microCi/kg) and bile was collected for up to 22 h. Biliary excretion accounted for 30% of the dose. No parent compound was detected in the bile. 4. In further studies, other rats were dosed p.o. or i.v. with 3H-Z-7760 (0.4 mg and 400 microCi/kg) and urine and faeces were collec...Continue Reading

References

Apr 1, 1974·The Journal of Pharmacy and Pharmacology·C F GeorgeD S Davies
Jan 1, 1981·Methods in Enzymology·G J MulderD K Meijer
Jan 1, 1997·Clinical and Experimental Hypertension : CHE·C SemeraroF Pocchiari

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Citations

Mar 15, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Akhmad Kharis NugrohoJoke A Bouwstra

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