MUPEg.com > Products > Gastroenterology > Pantoloc

Pharmacokinetics:

Pantoprazole:

	Is rapidly absorbed from the intestine.
	The peak plasma level is attained within 15- 20 minutes, with linear concentration of C_max of 2.5g/ml that occurs after single or multiple dose.
	Pantoprazole is well absorbed and it undergoes Little first- pass metabolism resulting in an absolute bioavailability of 77%.
	Pantoprazole absorption is not affected by concomitant administration of antacid or altered by food, thus pantoprazole may be taken without regard to timing of meals.

Distribution:

	The apparent volume of the absorbed pantoprazole is distributing mainly in the extra cellular fluid.
	The serum protein binding is about 98%, primarily to albumen.

Clinical Observations:
	"Following absorption, and quantitative tissue distribution , experiments have shown that pantoprazole is rapidly distributed to Extra vascular sites."

Metabolism:

	Pantoprazole is extensively metabolized in the liver 8. the main metabolic pathway is demethylation, by CYP 2C19.
	Subsequent sulfation and other metabolic pathways include oxidation by CYP 3A4.
	There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity. Also they have minimal accumulation (less than 23%) with the once daily dosing.

Elimination:

The elimination half-life is 1.1-3 hr.

Excretion:

About 80% of the dose was excreted in the urine with 20% excreted in feces through biliary excretion.

Pharmacodynamics:

Mechanism:

The drug is mainly accumulated in the acidic canaliculi of parietal cells where it is Converted in the pH<3 to the highly active form, sulfenamide species that bind the active site of H+/K+ATPase enzyme, result in a duration of anti secretory effect that persist longer than 24 hr.

The inactive (pro-drug) exerts its full effect only on the strongly acidic cells (pH < 3) and remains inactive at higher pH. Thus explains the drug high selectivity towards the acid secreting parietal cells.

Human Pharmacology:

Antisecretory Activity:

	The inhibitory action of pantoprazole persist till new acid is secreted and the pH becomes strongly acidic again. Without achlorhydria.
	Since the interaction is covalent and the half-life of the drug is more than 50 hours restoration of acid secretion necessities de novo biosynthesis of the ATPase enzyme.
	The level of its acid inhibition is more than 90% without achlorhayria. AND without rebound of hyper secretion after stopping the treatment for 7 days.
Clinical Observations:
	"There was no evidence of rebound hyper secretion OR Achlorhydria. Acid secretion had return to normal within a week after the last dose of pantoprazole."
	In a double –blind crossover study compared pantoprazole 40mg with omeprazole 20mg once daily for both one day and 7 days treatment periods, The result is greater increases in median pH during the 24 hr. with pantoprazole than did omeprazole.

Effects on the Serum Gastrin:

Following healing of gastric or duodenal ulcers with pantoprazole, the elevated gastrin levels return to normal by at least 3 months.

In a long term studies involving 800 patients

2-3 fold increase in the level of the pretreatment fasting serum gastrin level was observed in the initial months of treatment at dose of 40mg/ day.
In two double- blind studies in which 682 patients with GERD received 10,20 or40mg pantoprazole. At 4 and 8 weeks treatment there was an increase in the mean gastrin levels over the pre treatment levels.

Duration	10mg	20mg	40mg
4 Weeks	7%	35%	72%
8 Weeks	3%	26%	84%

Effects on the Enterrochromaffin-Like Cell:

In a clinical study on 39 patients with oral dose of 40-80mg for up to 5 years, There was a moderate increase in ECL-cell densty starting after the first year , and appeared to plateau after 4 years.

This explains the higher safety of pantoprazole over other PPI.

Other Effects:

No clinical relevant effects of Pantoloc on: Cardiovascular, Respiratory, Ophthalmic or Central Nervous Systems.

In a clinical pharmacology study, 40mg antoprazole was given once daily for 2 weeks, Pantoloc has no effect on the Level of the following hormones:

Cortisol
Testosterone
Triiodothyronin
T3
Thiroxine T4
Parathiroid hormon
Insulin
Glucagon
Renin
Aldosterone
Follicle-stimulating hormone
Prolactin
Growth hormone

This also explains the higher safety of pantoprazole over other PPI's.

Precautions:

Clinical pharmacological studies with pantoprazole show no induction or inhibition of human liver enzymes.

Hepatic Insufficiency:

Pantoprazole can be administered to patients with mild to moderate liver impairment unless the expected benefits outweigh the potential risks.

Renal Insufficiency:

No dose reduction is required when pantoprazole is administered to patients with impaired kidney function
as the difference in AUCs between patients who are dialyzed and those who are not is 4%.

Use in Pregnancy:

	There are no adequate or well-controlled studies in pregnant women.
	Pantoprazole is category B ; that should not be administered to pregnant women unless the expected benefits outweigh the potential risks to the fetus.

Use in Nursing Mothers:

It is not known whether pantoprazole is secreted in human milk. Pantoprazole sodium should not be given to nursing mothers unless its use is believed to outweigh the potential risks to the infant.

Use in Children:

The safety and effectiveness of pantoprazole sodium in children have not yet been established.

How Supplied:

Pantoloc 40:	40 mg/ 14 tablets 40 mg/ 7 tablets	For pepic ulcer treatment. For erosive esophagitis. for H. pylori eradication.
Pantoloc 20:	20 mg/ 14 tablets 20 mg/ 7 tablets	For heartburn. For other symptoms associated with GERD. For maintenance of healed esophagitis and peptic ulcer.