Pharmacokinetics of lansoprazole for injection in healthy volunteers

Objective: To establish an LC- MS /MS method for the determination of lansoprazole and its non- conjugated metabolites,5- hydroxy lansoprazole and lansoprazole sulphone in plasma and urine for the pharmacokinetic study of lansoprazole for injection in healthy Chinese volunteers. Methods: In a randomized,open label,three- way crossover study,12 healthy volunteers( 6 male and 6 female) were divided into three groups and administrated intravenously with a single dose of 15,30 and 45 mg of lansoprazole for injection,respectively,or multiple 30 mg doses for 7 consecutive days. The blood samples were collected at predetermined time points from 0 to 12 h and the urine samples in intervals from 0 to 24 h,and determined by the LC- MS /MS method. The pharmacokinetic parameters were estimated by DAS2. 0 software. Results: The LC- MS /MS method established showed linear calibration in the ranges of 10- 4000 μg·L- 1,2-400 μg·L- 1and 1- 400 μg·L- 1for lansoprazole,5- hydroxyl lansoprazole and lansoprzole sulphone in human plasma,respectively,and 4- 3200 μg·L- 1,0.8-320 μg·L- 1and 0. 4- 320μg·L- 1for lansoprazole,5- hydroxyl lansoprazole and lansoprzole sulphone in human urine,respectively. The intra- and inter- batch standard deviations were both less than 15%. After a single administration of 30 mg lansoprazole,the mean pharmacokinetic properties of lansoprazole,5- hydroxyl lansoprazole and Lansoprazole sulphone were as follows: Cmax( 1562 ±276) μg·L- 1,( 124.3 ±59.1) μg·L- 1and( 66. 03 ± 27. 3) μg·L- 1,respectively; tmax( 0.52 ±0. 050) h,( 2. 13 ±0.73) h and( 0.67 ±0.13) h,respectively; AUC0- τ( 2894 ±516) μg·L- 1·h,( 261. 3 ± 86. 0) μg·L- 1·h and( 121. 8 ±36. 7) μg·L- 1·h,respectively; t1 /2( 1. 56 ±0. 31) h,( 2. 13 ±0. 73) h and( 1. 49 ± 0. 40) h,respectively. After multiple administrations of 30 mg lansoprazole,the mean pharmacokinetic properties of lansoprazole,5- hydroxyl lansoprazole and lansoprazole sulphone were as follows: Cmax( 1555± 403) μg·L- 1,( 101.5 ±28.0) μg·L- 1and( 81. 06 ± 37. 5) μg·L- 1,respectively; Cmin( 14.59 ±4. 126)μg·L- 1,( 3.131 ±0.82) μg·L- 1and( 1. 046 ± 0. 61) μg·L- 1,respectively; tmax( 0.53 ±0.070) h,( 0. 67 ±0. 14) h and( 0. 70 ± 0. 17) h,respectively; AUC0- τ( 3031 ±830) μg·L- 1·h,( 244. 4 ±62. 5) μg·L- 1·h and( 166. 5 ± 84. 4) μg·L- 1·h,respectively; t1 /2( 1.68 ±0.39) h,( 2.01 ±0.65) h and( 1. 51 ±0.35) h,respectively. Only non- conjugated 5- hydroxy lansoprazole was found in urine with a cumulative excretory amount of( 2. 7 !1. 2) % in 24 hours. Linear pharmacokinetics was found after single intravenous dose of lansoprazole in the range of 15 mg to 45 mg without obvious gender differences. No cumulative effect was found after multiple 30 mg doses for 7 consecutive days. But one volunteer was found to have significantly different pharmacokinetic behavior( not included for ANOVA) from the others. Conclusion: The LC- MS /MS method established was accurate and suitable for the pharmacokinetic study of lansoprazole for injection. There was polymorphism in the metabolism of lansoprazole,therefore,therapeutic drug monitoring and individualized medication should be conducted for Lansoprazole clinical application.