AI Article Synopsis
- The study explored the pharmacokinetics of tenatoprazole, a new proton pump inhibitor, and its metabolites in 30 healthy male participants across varying doses.
- The research demonstrated that maximum plasma concentrations occurred 2.5 to 4.3 hours after administration, with a terminal half-life of 4.8 to 7.7 hours, and steady state was achieved after 5 days.
- While Cmax and AUC increased linearly for doses from 10 mg to 80 mg, the 120 mg dose resulted in unexpectedly higher Cmax, particularly at steady state, with similar linear increases for the metabolites TU-501 and TU-502 in the 40 to 120 mg range.
Article Abstract
The pharmacokinetics of tenatoprazole (CAS 113712-98-4), a newly synthesized proton pump inhibitor, and its metabolites TU-501 (sulfide form) and TU-502 (sulfone form) were investigated in an ascending-dose parallel-group study at the dose levels of 10, 20, 40, 80 and 120 mg. A total of 30 healthy Caucasian male volunteers (6 in each dose group) received a single dose at Day 1 (fasted state) and repeated doses from Day 14 to Day 20. CYP2C19 genotype status was determined in all subjects. Concentrations of tenatoprazole, TU-501 and TU-502 in plasma and urine were measured by a validated HPLC/MS/MS method. The single and multiple-dose study provided reliable tolerance. After the single administrations, plasma concentrations reached a maximum between 2.5 and 4.3 h post dose, and thereafter decreased according to a terminal half live (T1/2) ranging from 4.8 to 7.7 h. Similar T1/2 were obtained on first and the last administration, and the steady state was reached after 5 days. Cmax and AUC increased linearly between 10 to 80 mg. However, with the 120 mg dose, the observed Cmax was higher than expected, especially at steady state. For TU-501 and TU-502 metabolites, Cmax and AUC increased linearly after repeated administration between 40 and 120 mg.
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