Pharmacokinetic studies of mabuterol, a new selective beta 2-stimulant. I: Studies on the absorption, distribution and excretion in rats.

Pharmacokinetic studies on absorption, distribution, excretion and placental transfer of the beta-sympathomimetic 14C-labelled dl - 1 - (4 - amino - 3 - chloro - 5 - trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) have been carried out in rats. Mabuterol was easily absorbed from the whole length of the small intestine in a study in situ with the gastro-intestinal ligated loop technique. The blood and tissue levels of radioactivity reached the maximum within 1 h after oral administration. Concerning tissue distribution (excluding the digestive tract) after oral administration, the radioactivity in the liver, lung, kidney and several secretory organs was considerably higher than that in the blood. The levels of radioactivity in these tissues continued at almost the same levels for 2-6 h after oral administration, resulting from a slow gastric emptying of the radioactivity. The whole-body autoradiograms obtained after intravenous administration revealed the secretion of the radioactivity into the stomach. The radioactive concentration in the CNS was much lower than that in the principal organs with either route of administration. About 60% and 26% were excreted into urine and feces, respectively, within 24 h after oral administration. Although about 22% was excreted into bile within 24 h after intravenous administration, no other evidence of enterohepatic circulation was observed. The multiple oral administration of 14C-mabuterol indicated no, appreciable accumulation in the tissues of rats. A placental transfer in the pregnant rats in the last stage of gestation was not significant.