Safety, pharmacokinetics, and pharmacodynamics of S-(−)-pantoprazole sodium injections after single and multiple intravenous doses in healthy Chinese subjects

Abstract

Purpose

The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(−)-pantoprazole (PPZ) sodium injections following single and multiple intravenous doses in healthy Chinese subjects.

Methods

The dosage groups were set as followed: 20 mg of single and multiple intravenous administration of S-(−)-PPZ, 40 mg of single and multiple intravenous administration of S-(−)-PPZ or pantoprazole, and 80 mg of single dosage group of S-(−)-PPZ. Subjects were sampled for pharmacokinetic analysis and were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after administration for the pharmacodynamic study. The pharmacokinetic and pharmacodynamic parameters were compared between S-(−)-PPZ and PPZ. Safety was evaluated on the basis of adverse events, vital signs, laboratory tests, and physical examination.

Results

All adverse events were mild and of limited duration. Maximum plasma concentration and area under the concentration-time curve for S-(−)-PPZ were dose proportional over the range of 20–80 mg following a single intravenous administration. Elimination rate constant and half-life observed statistical difference from a single dose to multiple doses in 40 mg of S-(−)-PPZ groups. After administration of a single dose, the mean 24-h intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg groups. Slightly increase of intragastric pH was found after a single dose of 40 mg S-(−)-PPZ than 40 mg PPZ; however, the differences were not statistically significant.

Conclusions

Twice daily of 40 mg S-(−)-PPZ sodium injections is effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ levels, most subjects presented more potent and prolonged suppression of gastric acid of S-(−)-PPZ, while a few subjects showed faster metabolic rate of S-(−)-PPZ in vivo.

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