Metabolic disposition of thiazinamium chloride [N,N,N,α-tetramethyl(C3H3)-10H-phenothiazine-10-ethanammonium chloride] in rats and mice

The metabolic disposition of thiazinamium chloride (TC), a bronchodilator, was investigated in male rats (0.1 mpk, iv; 0.1 to 100 mg/kg, ig) and in mice (2.5 mg/kg, ig) receiving 3H labeled TC. In rats, the mean peak concentrations of radioactivity in plasma were low after intragastric dosings, ranging from less than 1 ng (0.1 mg/kg) to 337 +/- 27 (SD) ng (100 mg/kg) of drug equivalent/ml. Excretion of radioactivity in urine and feces (0-72 hr) ranged from 0.3 +/- 0.2 to 1.8 +/- and 91 +/- 1.8 to 99 +/- 1.5% of the dose, respectively. In contrast, the mouse (2.5 mg/kg, ig) showed a much higher mean peak concentration of radioactivity (734 +/- 658 ng of drug equivalent/ml) and substantially higher recovery of 3H (42% of the dose) in urine (0-72 hr). The major component excreted into rat urine (0-24 hr, 100 mg/kg, ig) was thiazinamium sulfoxide and the drug accounted for less than 5% of the urinary radioactivity, whereas in the mouse, thiazinamium ion and its sulfoxide accounted for about 50 and 30% of the urinary (0-24 hr) radioactivity, respectively. The low values in rats receiving intragastric doses were due to poor absorption and a first pass effect. Aerosol administration of the drug (0.3 and 2.4 mg/kg) to rats resulted in higher recoveries of thiazinamium ion (0.3 mg/kg - 7% and 2.4 mg/kg - 15% of the dose) in urine (0-48 hr post inhalation)