Pharmacokinetics of levetiracetam in healthy volunteers

OBJECTIVE To establish a HPLC method for determination of serum concentration of levetiracetam and to study the pharmacokinetics of the drug in healthy volunteers after single dose and multiple dose administration.METHODS Thirty-two volunteers were divided into four groups randomly,each group included four men and four women.In the single dose design,the volunteers of three groups received either a single dose of 250,500,750 mg levetiracetam.The volunteers of another group received 250 mg levetiracetam twice daily for 6 days.The serum concentrations were determined by HPLC method and the pharmacokinetic parameters of levetiracetam were calculated.RESULTS The main pharmacokinetics parameters of the drug after single oral dose of 250,500,750 mg were tmax:(1.4±1.2),(1.2±1.2),(1.8±1.1)h;Cmax:(7.2±1.7),(14.6±3.2),(20.2±4.9)mg·L-1;AUC0-36 :(61±11),(138±28),(202±35)mg·L-1·h;t1/2 :(5.5±0.8),(6.1±0.8)and(6.0±1.6)h.After oral dosing of 250mg twice daily for 6 days,the main pharmacokinetics parameters of the drug were tmax:(0.9±0.5)h,Cmax:(21.3±1.8)mg·L-1,Cmin:(7.5±1.7)mg·L-1,t1/2 :(5.8±0.9)h,Vd:(0.38±0.04)L·Kg-1,CL(0.046 0±0.000 5)L·h-1·Kg-1,AUCss:(138±9)mg·L-1·h,Cav:(11.5±0.8)mg·L-1.CONCLUSION The pharmacokinetic results show that levetiracetam exhibits first order kinetic characteristics.The pharmacokinetic parameters of levetiracetam do not differ remarkably after 500mg single and multiple doses and there is no accumulation in serum after oral dosing of 250 mg twice daily for 6days.