Preclinical investigation of the pharmacokinetic of a novel prolonged release dosage form of lithium citrate

Abstract

This study assessed the comparative pharmacokinetics of a novel prolonged release dosage form of lithium citrate in inbred mouse Unes BALB/c after single intragastrically administration. In the experiment mice were divided into two groups (8–10 animals each group) which were received Uthium citrate (LC) (75 mg/kg) or complex based on lithium citrate, aluminum oxide and organosilicone polymer (LCAS) (1120 mg/kg) once intragastrically. These doses were calculated based on lithium containing at the ratio 5,6 mg/kg. Pharmacokinetic parameters and relative bioavailability were calculated based on lithium ions concentration in serum and brain, which was measured by inductively-coupled plasma atomic emission spectrometry (ICP-AES). According to received pharmacological data the LCAS has a longer time period during which the lithium concentration exceeds 75% of the Cmax in compare with LC (Clast obs/Cmax of the new complex is 9.7 times more, than of standard LC substance), relative bioavailability of LCAS is 53.82% of standard LC. Maximum concentration of lithium ions is lower by 4,3 times, than if administration of LC. Performed research has proven that combining aluminium oxide and organosilicone polymer as supportive components with Uthium citrate helps to maintaining a stable Uthium ions concentration in blood and brain which is important for achieving positive lithium therapy effect.