The Physiological Disposition of the Anti-tussive Agent, 1, 2, 3, 4, 4a, 9b- Hexahydro-8, 9b-dimethyl-4- [3-(4-methylpiperazin-1-yl)propionamido]dibenzofuran-3-one Dihydrochloride Azipranone®, in Man, Rat, Dog and Baboon

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Abstract
1. The absorption, tissue distribution, elimination and biotransformation of the anti-tussive agent Azipranone® labelled with 14C have been investigated after oral dosing to rat, dog, baboon and man and parenteral administration to rat and baboon. 2. Levels of radioactivity in plasma were maximal within 20 min of dosing in the rat and after 1-2 h in the remaining species. The concn. declined thereafter with a half-life estimated at 1, 3-4 and 18-24 h for rat, dog, and baboon and man respectively. 3. Three human volunteers excreted 53, 62 and 70% of the radioactivity in the urine in 96 h while the remaining species excreted 50-70% of the dose in the faeces in the same period. 4. Radioactivity was rapidly and extensively eliminated in the bile of both rat and baboon after administration of [14C]Azipranone®. 5. The 24 h urine samples from all species contained ten major and a similar number of minor radioactive components. 6. In hepatic microsomal preparations, biotransformations of Azipranone® are catalysed by enzymes requiring both NADPH2 and cytochrome-P450.