Pharmacokinetics of tenatoprazole, a newly synthesized proton pump inhibitor, in healthy male Caucasian volunteers.
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.
Domagala
Florence
F
NEGMA-GILD, Magny les Hameaux, France.
Ficheux
Hervé
H
Houin
Georges
G
Barré
Jérôme
J
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001711:Biotransformation; D065731:Cytochrome P-450 CYP2C19; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D005838:Genotype; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D009853:Omeprazole / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004791:Enzyme Inhibitors; D007093:Imidazoles; D054328:Proton Pump Inhibitors; D011725:Pyridines; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; C119998:Tenatoprazole