Physiological disposition of oral piracetam in Sprague-Dawley rats

The distribution and fate of piracetam (2-oxo-1-pyrrolidine acetamide, Nootropil), the prototype 'nootropic drug', was examined in rats given 100-1000 mg kg-1 by gavage, with or without [3H]piracetam as a tracer. Peak serum concentrations were attained after 60 min. Its half-life of disappearance from serum was about 2 h during the initial 8 h after administration and then about 6.4 h for the next 16 h. Brain piracetam concentrations equilibrated with those of serum at about 4 h, after which they fell exponentially but remained about twice those of serum; piracetam concentrations in the brainstem were lower (by 30-40%) than those in the cortex, olfactory bulb, and colliculi. No evidence could be obtained for significant piracetam metabolism, either in-vivo or when incubated with liver homogenates. No specific binding of [3H]piracetam to any of various subcellular fractions was observed after its administration along with unlabelled carrier. Repeated daily doses of piracetam (7 days, 100 mg kg-1) failed to elevate serum or brain concentrations beyond those observed after a single dose.