Metabolic disposition of Rolziracetam in laboratory animals

The metabolic disposition of [14C]-labeled Rolziracetam (CI-911) was studied in rhesus monkeys, beagle dogs, and Wistar rats after both p.o. and i.v. doses. Intravenously administered CI-911 was rapidly eliminated from systemic circulation with an apparent elimination half-life of less than 25 min. Plasma radioactivity was 10-20 times higher than that of parent drug and persisted much longer. After oral doses, only traces of intact drug were detected in plasma, whereas total radioactivity reached peak concentrations within 0.5-1 h indicating rapid absorption. The extent of absorption determined from plasma radioactivity and urinary excretion data was 90% or better. Tissue distribution of radioactivity in rats showed the highest concentrations in the liver and kidneys (12-30 times greater than plasma levels) with decreasing levels in the lungs, gonads, heart, spleen, muscle, and brain. Urinary excretion accounted for nearly 90% of the administered dose while fecal recovery was less than 5%. The sole metabolite present in plasma, tissues, and urine was identified as 5-oxo-2-pyrrolidinepropanoic acid (PD 106,687).