Pharmacokinetics of huperzine A in rats and mice

Huperzine A, a new alkaloid first isolated in China from Huperzia serratacl), is a reversible cholinesterase inhibitor). Clinical studies have shown that huperzine A can improve muscle weakness of myasthenia gravis(s) and memory function in patients of cerebral arteriosclerosis with memory impairment. The blood level of huperzine A following iv or ig [3H] huperzine A 13.9 MBq/kg in rats declined in two phases, the distribution phase and the elimination phase, with half-lives of 6.6; 149 min (iv) and 10; 203 min (ig) respectively. The pharmacokinetic parameters were calculated according to the 2-compartment open model. In mice 15 min after iv [3H]huperzine A 9.25 MBq/kg, the radioactivities were highest in the kidney and liver. moderate in the spleen, lung and heart, and lower in brain. In pregnant mice, the small amount of radioactivity was shown in the fetus after iv [3H]huperzine A. The drug-plasma binding rate was found to be 17%. The majority (73%) of the radioactivity was excreted in the urine 24h after iv [3H] huperzine A 9.25 MBq/kg in mice, while only 2.4% was recovered from the feces. Paper chromatograms of urine revealed that [3H]huperzine A was excreted partially as prototype and its metabolite respectively.