ABSTRACT
AIM: To evaluate the pharmacokinetics and pharmacodynamics of (S)-pantoprazole sodium enteric-coated tablets in healthy subjects by using pantoprazole sodium enteric-coated tablets as a control drug. METHODS: Thirty healthy Chinese subjects were enrolled in a randomized, open and positive control trial. The subjects were given 20 and 40 mg (S)-pantoprazole sodium enteric-coated tablets and 40 mg pantoprazole sodium enteric-coated tablets, respectively. The concentration of (S)-pantoprazole in the human plasma was determined by LC-MS/MS and the pharmacokinetic parameters were calculated by WinNonlin 6.4 software. The intragastric pH was monitored for 24 hours. The dose-effect relationship of drugs was evaluated. RESULTS: The main pharmacokinetic parameters of (S)-pantoprazole after single administration of 20 and 40 mg (S)-pantoprazole sodium and 40 mg pantoprazole sodium enteric-coated tablets were as follows: The Cmax were (1 635±410), (2 756±1 024) and (1 536±615) ng/mL, the t1/2 were (1.41±0.31), (1.55±0.64) and (1.35±0.22) h, the AUC0-t were (3 623±1 322), (7 383±3 785) and (3 276±1 302) h•ng•mL-1; The main pharmacokinetic parameters of multiple administration were as follows: The Cmax were (1 704±239), (3 297±743) and (1 832±557) ng/mL, the t1/2 were (1.41±0.40), (1.58±0.64) and (1.45±0.22) h, the AUC0-t were (3 587±1 040), (8 189±3 399) and (3 878±1 272) h•ng•mL-1. After the treatment, the time of pH>4.0 as a percentage of total time (%) after single administration were (32.98±10.7)%, (45.37±9.61)% and (32.63±14.63)%; and the time of pH>4.0 as a percentage of total time (%) after multiple administration were (45.12±11.97)%, (50.76±10.63)% and (41.67±7.1)%. CONCLUSION: Healthy subjects have linear kinetic characteristics of (S)-pantoprazole after single and multiple administrations, and the 40 mg (S)-pantoprazole sodium group has better efficacy than other dose groups. Healthy subjects were well tolerated.