Comparative pharmacokinetic/pharmacodynamic analysis of proton pump inhibitors omeprazole, lansoprazole and pantoprazole, in humans

Katashima, Masataka; Yamamoto, Keiji; Tokuma, Yoji; Hata, Takehisa; Sawada, Yasufumi; Iga, Tatsuji

doi:10.1007/bf03189822

Cited by 59 publications

(74 citation statements)

References 22 publications

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“…The above data are consistent with the slower recovery of acid secretion after pantoprazole inhibition as compared to that after omeprazole inhibition deduced from human data [9,23]. Whether this stability of labeling after pantoprazole labeling produces a clinical benefit, particularly in diminishing nocturnal acid breakthrough and night time GERD, remains to be established.…”

Section: Biology Of Proton Pump Inhibitorssupporting

confidence: 81%

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The gastric HK-ATPase: structure, function, and inhibition

Shin

Munson

Vagin

et al. 2008

Pflugers Arch - Eur J Physiol

219

181

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The gastric H,K-ATPase, a member of the P 2 -type ATPase family, is the integral membrane protein responsible for gastric acid secretion. It is an α,β-heterodimeric enzyme that exchanges cytoplasmic hydronium with extracellular potassium. The catalytic α subunit has ten transmembrane segments with a cluster of intramembranal carboxylic amino acids located in the middle of the transmembrane segments TM4, TM5,TM6, and TM8. Comparison to the known structure of the SERCA pump, mutagenesis, and molecular modeling has identified these as constituents of the ion binding domain. The β subunit has one transmembrane segment with N terminus in cytoplasmic region. The extracellular domain of the β subunit contains six or seven Nlinked glycosylation sites. N-glycosylation is important for the enzyme assembly, maturation, and sorting. The enzyme pumps acid by a series of conformational changes from an E 1 (ion site in) to an E 2 (ion site out) configuration following binding of MgATP and phosphorylation. Several experimental observations support the hypothesis that expulsion of the proton at 160 mM (pH 0.8) results from movement of lysine 791 into the ion binding site in the E 2 P configuration. Potassium access from the lumen depends on activation of a K and Cl conductance via a KCNQ1/KCNE2 complex and Clic6. K movement through the luminal channel in E 2 P is proposed to displace the lysine along with dephosphorylation to return the enzyme to the E 1 configuration. This enzyme is inhibited by the unique proton pump inhibitor class of drug, allowing therapy of acid-related diseases.

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Section: Biology Of Proton Pump Inhibitorssupporting

confidence: 81%

“…An analysis of the rate of restoration of acid secretion in man after omeprazole inhibition suggested that the halftime was 24 h, whereas after pantoprazole, it was 46 h [12]. Apparently, only the latter drug gave a rate of recovery compatible with restoration of acid secretion as due entirely to pump turnover [9,23].…”

Section: Biology Of Proton Pump Inhibitorsmentioning

confidence: 99%

The gastric HK-ATPase: structure, function, and inhibition

Shin

Munson

Vagin

et al. 2008

Pflugers Arch - Eur J Physiol

219

181

View full text Add to dashboard Cite

show abstract

“…The above data are consistent with the slower recovery of acid secretion following pantoprazole inhibition as compared to that following omeprazole inhibition deduced from human data [60,61]. Whether this stability of labeling following pantoprazole labeling produces a clinical benefit, particularly in diminishing nocturnal acid breakthrough and nocturnal GERD, remains to be established.…”

Section: Restoration Of Acid Secretion After Ppi Inhibitionsupporting

confidence: 78%

“…In other experiments, the halftime of restoration of acid secretion in omeprazole-treated rats was 20 h [58,59]. Analysis of the rate of restoration of acid secretion in humans following omeprazole suggested that the half-time was 24 h whereas after pantoprazole it was 46 h. Apparently, only the latter drug gave a rate of recovery compatible with restoration of acid secretion entirely from pump turnover [60,61].…”

Section: Restoration Of Acid Secretion After Ppi Inhibitionmentioning

confidence: 98%

Molecular mechanisms in therapy of acid-related diseases

Shin

Vagin

Munson

et al. 2007

Cell. Mol. Life Sci.

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Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogenpotassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists.

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“…However, acid secretion and H,K-ATPase activity returned with a half-life of only 15 hr in this species, about three times faster than anticipated if only protein turnover were responsible for recovery of acid secretion. Following treatment of people with PPI's, acid secretion also returns faster than expected from protein turnover for omeprazole or lansoprazole (~20 hr) [60]. Only pantoprazole has a duration of action compatible with recovery due only to pump biosynthesis (~47 hr).…”

Section: Reversal Of Acid Secretory Inhibitionmentioning

confidence: 99%