| Reference | 1. Arzneimittelforschung. 2006;56(1):33-9.
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Pharmacokinetics of tenatoprazole, a newly synthesized proton pump inhibitor, in
healthy male Caucasian volunteers.
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Domagala F(1), Ficheux H, Houin G, Barré J.
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Author information: <br>
(1)NEGMA-GILD, Magny les Hameaux, France.
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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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2. Aliment Pharmacol Ther. 2004 Mar 15;19(6):655-62.
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Tenatoprazole, a novel proton pump inhibitor with a prolonged plasma half-life:
effects on intragastric pH and comparison with esomeprazole in healthy
volunteers.
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Galmiche JP(1), Bruley Des Varannes S, Ducrotté P, Sacher-Huvelin S, Vavasseur F,
Taccoen A, Fiorentini P, Homerin M.
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Author information: <br>
(1)CIC-INSERM, CHU de Nantes, Nantes, France. [email protected]
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BACKGROUND: Proton pump inhibitors control gastric acidity better during the day
than at night, when nocturnal acid breakthrough can occur. Tenatoprazole is a
novel proton pump inhibitor with a seven-fold longer plasma half-life. Aim : To
compare the effects of tenatoprazole 20 mg (T20), tenatoprazole 40 mg (T40) and
esomeprazole 40 mg (E40) on intragastric acidity in healthy volunteers.
METHODS: This randomized, three-period, cross-over study enrolled 18 Helicobacter
pylori-negative volunteers, who received E40, T20 and T40 once daily for 7 days
with a 14-day washout between periods. Twenty-four-hour gastric pH monitoring was
performed on day 7. Serum gastrin was assessed on day 8.
RESULTS: T40 induced a more potent acid inhibition than T20 (24-h median pH: 4.6
vs. 4.0, P < 0.01; daytime: 4.5 vs. 3.9, P < 0.01; night-time: 4.7 vs. 4.1, P <
0.05). T40 was more potent than E40 (24-h median pH: 4.6 vs. 4.2, P < 0.05;
night-time: 4.7 vs. 3.6, P < 0.01); the pH > 4 holding time was higher during the
night for T40 than for E40: 64.3% vs. 46.8%, P < 0.01; the nocturnal acid
breakthrough duration was significantly shorter for T40 than for E40. No
significant gastrin increase was observed and all drugs were well tolerated.
CONCLUSION: T40 is significantly more potent than T20 and E40 during the night.
The therapeutic relevance of this pharmacological advantage deserves further
study.
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