Pharmacokinetics of Lansoprazole Injection in Chinese Healthy Volunteers

OBJECTIVE To establish a HPLC method for the determination of lansoprazole in human plasma and determine the pharmacokinetics of lansoprazole.METHODS Lansoprazole and internal standard phenacetin were extracted from plasma with ether.The content of lansoprazole was detected by ultraviolet detector at 285 nm with Kromasil 100-5 C8(4.6 mm×150 mm) column.The mobile phase consisted of water-acetonitrile-diethylamine(adjusted to pH 6.7 with H3PO4)(600∶400∶1.2)at a flow rate of 0.8 mL·min-1.The column temperature was 40 ℃.A single-dose,open-label,randomized,three-period crossover dose study was carried out in 12 healthy volunteers.The subjects received intravenous infusion of 15,30 and 60 mg lansoprazole.The concentrations of lansoprazole in plasma were determined by HPLC method and the pharmacokinetic parameters were calculated.RESULTS The linear range was 49.0 to 4 900.0 ng·mL-1(r=0.999 9).The lowest quantitive concentration was 49.0 ng mL-1(S/N 10).The average method recovery was 93.3% to 100.1%,and extracted recovery was over 82% for the low,middle,high control samples.The main pharmacokinetic parameters of the three groups(15,30 and 60 mg) were as follows:ρmax(1 105.65±506.24),(2 171.33±799.02) and(4 070.53±643.04) ng·mL-1,tmax(0.24±0.14),(0.51±0.16) and(1.02±0.07)h,t1/2(3.01±1.77),(3.98±2.51) and(3.73±1.55)h,MRT0-12(0.93±0.95),(1.91±0.83) and(2.42±0.65)h,AUC0-12(991.16±814.49),(3 495.87±1 770.92),(8 351.14±2 599.90) ng·h ·mL-1.CONCLUSION This method is convenient,sensitive and reproducible,suitable for the determination of lansoprazole in human plasma for pharmacokinetics.Within the lansoprazole administration limit of 15-60 mg,the linear character of pharmacokinetics is showed in the body,which conforms to the two compartment models.