An informative but short explanation of one of the important PPI pantoprazole. I hope it will help you to make enough sense about pantoprazole. Be connected with me. Thank you .

1. Abir Hasan Sajid
Student
Dept of Pharmacy
Jashore university of science and technology
By…
Pantoprazole

2. Molecular
Machanism
Side
effects
Introduction
Drug
Interaction
Pharmaco
kinetics
Metabolism
Dose,dosage
form ,strength
Contents
Indication
Precaution,
contraindication

3. Introduction
Inhibits H+/K+ ATPase enzyme(proton pump)
Prodrug
(requires activation)
Reduce Gastric
acid secretion
Chemical structure of Pantoprazole
Pantoprazole is a proton pump inhibitor that suppresses the final step in gastric
acid production by covalently binding to the H+/K+ATPase enzyme system at the surface
of the gastric parietal cell. H+/K+ ATPase is nothing but proton pump.
Treat Ulcer,GERD
Known as
Proton pump
inhibitor (PPI)

4. Pyridine ring
Benzimidazole ring
Structure of pantoprazole
Pyridine
-prazole
Benzimidazole
Two types of heterocylic ring connected with alkyle sulphoxide bridge in the Structure of
Pantprazole. The suffix –prazole is derived from that two ring name.
1. Benzimidazole (Indicates azole of the suffix prazole)
2. Pyridine (Indicates pr of the suffix prazole)
Introduction

5. Molecular mechanism
◾Mechanism of acid secretion in stomach
H2O+CO2
CA
H2CO2
HCO3
-
H+
K+
PP
Cl-
Cl- H+
HCO3
-
HCl
Within the gastric parietal cells, water and CO2 combine and produce t
he carbonic acid by carbonic anhydrase enzyme.
Then carbonic acid split into carbonate ion and proton
Bicarbonate exchange outside with Chloride ion by another pump
The chloride ion directly s
ecrete into lumen
Proton secrete into lumen by
proton pump exchange of
potassium ion
Poton and chloride combines
and produce HCl acid

6. Pantoprazole is a pro-drug. So it requires bioactivation. After adminstration, it Converted
into a active Metabolite. It is actually responsible for the inhibiting proton pump.
NB: Prodrug is a biological inactive compound which need to be metabolized in the body to
form a active drug.
2H+
Process of bioactivation
Step 1: Two nitrogen of the two ring of Pantoprazole are attacked by the proton.
Pantoprazole
Molecular mechanism
Protonated Pantoprazole

7. Step 2: The protonated Pantoprazole loses proton and one nitrogen form a bond with carbon
of benzimidazole ring. Sulfer breaks the bond with the same carbon and form –S–OH group.
-H+
Molecular mechanism
-SH -SH
Step 3: This –S-OH complex of Pantoprazole loses water and form a amide bond with
benzimidazole‘s Nitrogen and make Sulfenamide (Active metabolite of Pantoprazole).
Sulfenamide(active drug)
-H20

8. Molecular mechanism
◾How Acid secretion inhibited by pantoprazole
Pantoprazole enters into gastric parietal cell
Convert into active metabolite (Sulfenamide)
Sulfenamide interact with proton pump
Sulfenamide bind to proton pump at thial group
Proton pump cant pass proton to the lumen
HCl formation inhibited in Gastric environment
Inactive
Pantoprazole
Active drug
-

9. The active form of pantoprazole(sulfenamide) binds covalently to the gastric H+/K+-ATPase
enzyme via disulfide bond.
Reaction occurs with Cys813 and Cys822 Site of H+/K+ ATPase enzyme at thial group(-SH) and form
stable disulfides.
Sulfenamide reaction with the ATPase enzyme inhibited the enzyme and it can’t pass proton and
potassium betweens lumen and cell.Thus HCl cant be formed in lumen.
Molecular mechanism
Sulfenamide
◾How pantoprazole reacts with H+/K+ ATPase enzyme
Proton pump
Cysteine
S
Sulfenamide – proton pump complex
H+/K+ ATPase(proton pump)

10. Indications
The main indication of Pantoprazole is Gastric ulcer. It reduce gastric acid secretion and protects the g
astric wall from being wounded.
It can treat gastro esophagus reflux disorder by reducing gastric acid secretion. Where gastric acid
reflux into esophagus.
It is prescribed with NSAIDs. Because NSAIDs increase gastric acid secretion.
In triple and quadrupole therapy, It can treat infection in the gastric wall caused by a gram –ve bacteri
a named Helicobacter pylori.
It reduced acid secretion caused by zollinger addisons sundrome in which tumor cause stomach to
produce more acid.
It can be used as prophylactic after anesthesia.
It can be used in the treatment of dyspepsia.

11. Indications
Gastric Ulcer
Gastro esophagus
reflux disorder
With NSAIDs
Helicobacter-
pylori eradication
Zollinger ellison
syndrome
Pantoprazole

12. Drug Interaction
PPI‘s are generally inhibit the CYP450 enzyms and one of the important CYP450 enzyme
on which PPI’s act is CYP2C19.
Some drugs are activated by this enzyme. Such as Clopidogrel,Nelfinavin,Rilpirivine.
So when these drugs are adminstrated with PPI’s,these drug‘s metabolism can be inhibited
by the PPI’s that is mainly for the inhibition of enzyme CYP2C19. Though pantoprazole is less
inhibitory among the other PPI’s
Drugs that affect by the alteration of pH of upper GI tract should be contraindicated.
Pantoprazole may alter the solubility and absorption by altering pH.
Example: Erlotinib,Nelfinavir.
Pantoprazole CYP2C19 Inhibited CYP2C19
Nelfinavir Inhibited CYP2C19
Reduced
Nelfinavir effectActive M8 metabolite

13. Half-life: 1 hr; increased to 3.5-10 hr wit
h
CYP2C19 deficiency
Dialyzable: No
Renal clearance: 0.1 L/hr/kg
Total body clearance: 7.6-14 L/hr
Excretion: Urine (71%); feces (18%)
Pharmacokinetics(ADME)
Absorption
Bioavailability: 77% (PO; neither food
nor
antacid alters bioavailability)
Onset (PO PUD): 24 hr (initial response
)
Duration (PO at steady state): 7 days
(PUD)
Peak plasma time: 2.8 hr (PO); at end
of
infusion
Protein bound: 98%
Vd: 11-24 L
Metabolized extensively by hepatic P4
50
enzyme CYP2C19.
Plasma concentration can increase by
5-fold or more in comparison with that
found in persons who have the enzym
e.
Metabolites: Desmethylpantoprazole
sulfate conjugate (activity unknown)
Absorption
Distribution
Metabolism
Excretion

14. Pantoprazole
sulfone Pantoprazol
sulfide
5-hydroxy
pantoprazole
Pantoprazole
sulphate
sulfone
Pantoprazole
sulphate
sulfide (M3)
CYP3A4CYP2C19
CYP3A4
Sulfo-
transferase
Metabolism
PPIs are enzymatically cleared in
the liver by demethylation reaction
primarily by the cytochrome P450 2C19
(CYP2C19) enzyme, and to a lesser
extent by CYP3A4(oxidation).
Metabolites:
5-hydroxy pantoprazole,Pantoprazole
sulphate, pantoprazole sulfone,
pantoprazole sulphate sulfone,
pantoprazole sulphide,pantoprazole
sulphate sulphide.
It is documented that CYP2C19 is
responsible for > 80% of the metabolism
of pantoprazole metabolism.
Pantoprazole
CYP3A4
Pantoprazole
sulphate
(M2)
CYP3A4

15. Dose,Dosage form and Strength
Oral suspension
•40mg/packet
Powder for injection
•40mg/vial
Tablet(delayed-release)
•20mg / 40mg
Tablet(Immediate release)
•40mg
Indications Dose(Tabletl Time Dose (Iv injection) Time
GaStric Ulcer 40 mg(Daily morning)
For 4 weeks / 8 weeks
(if not healed)
40mg once daily For 7-10 days
GERD
20-40 mg
(daily morning)
For 4 weeks /8 weeks
(if not healed)
40mg once daily For 7-10 days
Zollinger ellison
syndrome
80 mg daily
(adjusted)
Variable
80 mg every 12 hours
(Variable)
Variable
Prophylaxis for NSAID 20 mg daily
According to
NSAID
80mg every 12 hours For 24 hours
H-pylori ulcer
40 mg twice daily
associated with
antimicrobials
According to
antimicrobials
- -

16. Side effects
Side
effects
Vomiting
Headache
Nausea
Abdom-in
al pain
Vit-B12
deficiency
Allergic
reaction
Diarrhoea
Bone
fracture
Long term uses (over 3 years) can
cause vit-B12 deficiency(Numbness,
weakness) and also has probability
of bone fracture.
Headache
Main side effects of Pantoprazole is
nausea,vomiting(4%), Headache(12%)
Diarrhoea(9%), dizziness(3%),
abdominal pain(6%), joint pain(3%)
Abdominal pain

17. Precaution and warnings!
Contraindication
Patients should be cautioned that Pantoprazole tablet should not be split, chewed or crushed.
Long-term therapy of Pantoprazole may lead to malabsorption of cyanocobalamin (Vitamin B12)
Long-term therapy may increase the risk of osteoporosis related disorders.
Pantoprazole is contraindicated in patients with known hypersensitivity to any of the
components of the formulation.
It is also contraindicated when given with the pH sensitive drugs.
◾Erlotinib
◾Nelfenavir

18. Reference
https://reference.medscape.com/drug/protonix-pantoprazole-342001#10
https://www.sciencedirect.com/topics/chemistry/pantoprazole
https://www.pediatriconcall.com/drugs/pantoprazole/850
https://youtu.be/V0HR-ojkURw
https://medex.com.bd/generics/859/pantoprazole/brand-names
https://en.m.wikipedia.org/wiki/Pantoprazole