RESUMEN
A radioimmunoassay procedure for the determination of pirenzepine in either plasma or urine was demonstrated to be both sensitive and specific as well as highly reproducible. The assay could detect levels as low as 1.25 ng/ml. The sensitivity was sufficient to allow the analysis of biological samples from both pharmacokinetic and clinical studies. The two metabolites of pirenzepine, LS 75 and LS 822, did not cross-react with the antiserum. The assay was not affected by a change in anticoagulant or by the presence of several over-the-counter or prescription drugs, even at very high levels. Samples could be frozen and stored for at least a year without affecting the analysis. Repeat analysis could be performed on samples that had been refrozen. Several thousand plasma and urine samples, including plasma samples from severely renally impaired patients, have been analyzed for pirenzepine by the RIA with no interferences having been detected.
Asunto(s)
Pirenzepina/análisis , Animales , Anticoagulantes , Reacciones Cruzadas , Estabilidad de Medicamentos , Congelación , Humanos , Preparaciones Farmacéuticas/análisis , Pirenzepina/análogos & derivados , Conejos , RadioinmunoensayoRESUMEN
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.
Asunto(s)
Antihipertensivos/metabolismo , Morfolinas/metabolismo , Animales , Antihipertensivos/orina , Pruebas Respiratorias , Dióxido de Carbono/metabolismo , Cromatografía en Capa Delgada/métodos , Perros , Heces/análisis , Masculino , Distribución TisularRESUMEN
A reliable, sensitive, and specific radioimmunoassay (RIA) procedure for the quantitation of clonidine in plasma and other biological fluids was developed. The detection limit of the assay is 2 pg based on a 200 microliters sample. Nine commonly used drugs were found not to interfere with the RIA. The utility of the assay was demonstrated in a bioavailability study of clonidine conducted with 24 healthy subjects. Clonidine was readily quantitated in plasma over 4 half-lives. This assay is suitable for pharmacokinetic and bioavailability studies as well as therapeutic drug monitoring of patients.