Tissue distribution and excretion in urine, feces and respiratory CO2 of [14C]-ciclosidomine in beagle dogs.
14C-Labelled N-cyclohexanecarbonyl-3-(4-morpholino)-sydnone-imine hydrochloride [( 14C]-ciclosidomine, Neopres) labelled in the sydnone or morpholine position was administered orally and by intravenous injection to beagle dogs at a dose level of 1 mg/kg. The rates and routes of excretion of radioactivity were determined. The oral dose was completely absorbed and most (greater than 70%) of the radioactive label (both positions) was excreted in the urine within the first 24-48 h. The remaining label(morpholine-labelled drug) was found in feces (less than or equal to 8%), respiratory 14CO2 (2.3%) and throughout the carcass, with no major single depot. Radioactivity peaked within four hours. Elimination of dose label from the blood was biphasic, with an alpha phase (t 1/2 of 2.5 and 4.6 h after oral administration of morpholine- and sydnone-labelled drug, respectively) and a very slow beta-phase (t 1/2 = 120 h, both labels). Thin layer chromatography of 0-24 h urines (morpholine label) indicated total metabolism of the parent compound. A device is described for the continuous monitoring over several days of 14CO2 in exhaled breath from a conscious dog.
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism* / Q000652:urine; D001944:Breath Tests; D002245:Carbon Dioxide / Q000378:metabolism; D002855:Chromatography, Thin Layer / Q000379:methods; D004285:Dogs; D005243:Feces / Q000032:analysis; D008297:Male; D009025:Morpholines / Q000378:metabolism*; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D009025:Morpholines; D002245:Carbon Dioxide; C045064:ciclosidomine