| Indication |
Short-term (up to 16 weeks) treatment of erosive esophagitis. |
| Pharmacodynamics |
Pantoprazole is a substituted benzimidazole indicated for the
short-term treatment (up to 16 weeks) in the healing and symptomatic
relief of erosive esophagitis. Pantoprazole is a proton pump inhibitor
(PPI) that suppresses the final step in gastric acid production. |
| Mechanism of action |
Pantoprazole is a proton pump inhibitor (PPI) that suppresses the
final step in gastric acid production by forming a covalent bond to two
sites of the (H+,K+ )- ATPase enzyme system at the
secretory surface of the gastric parietal cell. This effect is dose-
related and leads to inhibition of both basal and stimulated gastric
acid secretion irrespective of the stimulus. |
| Absorption |
Pantoprazole is well absorbed. It undergoes little first-pass
metabolism resulting in an absolute bioavailability of approximately
77%. |
| Volume of distribution |
|
| Protein binding |
98% |
| Metabolism |
Pantoprazole is extensively metabolized in the liver through the
cytochrome P450 (CYP) system. The main metabolic pathway is
demethylation, by CYP2C19, with subsequent sulfation; other metabolic
pathways include oxidation by CYP3A4. There is no evidence that any of
the pantoprazole metabolites have significant pharmacologic activity. |
| Route of elimination |
After administration of a single intravenous dose of 14C-labeled
pantoprazole to healthy, normal metabolizer subjects, approximately 71%
of the dose was excreted in the urine with 18% excreted in the feces
through biliary excretion. |
| Half life |
1 hour |
| Clearance |
|
| Toxicity |
Single intravenous doses of pantoprazole at 378, 230, and 266
mg/kg (38, 46, and 177 times the recommended human dose based on body
surface area) were lethal to mice, rats and dogs, respectively. The
symptoms of toxicity included hypoactivity, ataxia, hunched sitting,
limb-splay, lateral position, segregation, absence of ear reflex, and
tremor. There is limited experience regarding cases of human overdosage,
and treatment should be symptomatic and supportive. |
