Comparison of the gastric acid inhibition function among lansoprazole, pantoprazole, and their respective stereoisomers in healthy Chinese subjects
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OBJECTIVE: This study was conducted to evaluate the difference in acid inhibition function among lansoprazole (LPZ), pantoprazole (PPZ), and their respective stereoisomers following single and multiple intravenous doses in healthy Chinese subjects. MATERIALS AND METHODS: The dosage groups were set as follows: 30 mg single and multiple intravenous administrations of LPZ or R-LPZ, 40 mg single and multiple intravenous administrations of PPZ or S-PPZ. Subjects received an intravenous infusion of LPZ, R-LPZ, PPZ, or S-PPZ injection in sterile saline solution (100 mL/h, 60 minutes), respectively. The intragastric pH was sampled every second for 24 hours at baseline and for 24 hours after drug administration. The baseline-adjusted pharmacodynamic (PD) parameters include ΔMean (pH), ΔMedian (pH), ΔTpH≥3 (%), ΔTpH≥4 (%), ΔTpH≥6 (%), and ΔAUECph-tτ1-τ2. The PD parameters were evaluated in different time intervals (0 - 24 hours, 0 - 4 hours and 14 - 24 hours). RESULTS: After a single dose, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ and PPZ was 56.6 ± 19.6, 53.1 ± 23.3, 35.6 ± 24.9 and 26.8 ± 30.2, respectively. The ΔTpH≥6 (%) was 50.7 ± 26.1, 41.4 ± 26.2, 25.4 ± 24.9 and 22.1 ± 27.6, respectively. The ΔAUECph-τ1-τ was 45,564 ± 16,107, 41,798 ± 16,153, 31,914 ± 17,304 and 20,744 ± 21,500, respectively. Statistically significant differences were found with R-LPZ vs. S-PPZ, R-LPZ vs. PPZ, LPZ vs. S-PPZ and LPZ vs. PPZ. The average TpH≥4 of R-LPZ, LPZ, S-PPZ, and PPZ was (47.2 ± 26.1) minutes, (49.6 ± 19.3) minutes, (56.1 ± 23.7) minutes, and (72.1 ± 27.3) minutes, respectively. Statistically significant differences were found with R-LPZ vs. PPZ (p = 0.009) and LPZ vs. PPZ (p = 0.019). After multiple doses, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ, and PPZ was 71.7 ± 20.2, 63.5 ± 19.4, 59.5 ± 17.8 and 64.0 ± 22.4, respectively. The ΔTpH≥6 (%) was 64.0 ± 22.2, 52.0 ± 19.2, 49.6 ± 20.4 and 50.9 ± 23.8, respectively. The ΔAUECph-τ1-τ was 326,149 ± 94,839, 288,565 ± 93,279, 296,189 ± 83,412 and 300,960 ± 108,057, respectively. No statistically significant differences were found in baseline-adjusted PD parameters during all time periods after multiple doses. CONCLUSION: After a single dose, the mean gastric pH inhibition value of R-LPZ was the highest, followed by LPZ, then S-PPZ and PPZ. R-LPZ and LPZ provided significantly better pH control compared with PPZ and S-PPZ in healthy subjects. The onset time of R-LPZ was the fastest and R-LPZ can provide better acid inhibition during sleeping time. After multiple doses, the mean values in all PD parameters of R-LPZ were the highest, the values of LPZ, S-PPZ, and PPZ were similar. However, no significant difference was found in acid inhibition among these four drugs after multiple doses.