Jashore University of Science and Technology
Department of Pharmacy
Course title: Human Physiology and Anatomy-IV
Course code: Phar-2209
An assignment
on
Pantoprazole
Submitted by Submitted to
Name: Abir Hasan Sajid Md Nazmul Hasan Zilani
ID: 181035 Lecturer
2nd year, 2nd semester Department of Pharmacy
Session: 2018-19 Jashore University of Science and
Department of Pharmacy Technology
Jashore University of Science and
Technology
Molecular
Introduction Machanism
Indication
Side
effects
Pharmaco
Contents kinetics
Drug
Interaction
Dose,dosage
form ,strength
Precaution,
contraindication Metabolism
Introduction
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.
Inhibits H+/K+ ATPase enzyme(proton pump)
Known as
Prodrug
Proton pump
(requires activation)
inhibitor (PPI)
Reduce Gastric Treat Ulcer,GERD
acid secretion
Chemical structure of Pantoprazole
Introduction
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)
Pyridine ring
-prazole
Benzimidazole ring Pyridine Benzimidazole
Structure of pantoprazole
Molecular mechanism
◾Mechanism of acid secretion in stomach
Within the gastric parietal cells, water and CO2 combine and produce t
he carbonic acid by carbonic anhydrase enzyme. HCO 3-
Cl - HCO3- H 2 O+CO2
Then carbonic acid split into carbonate ion and proton
CA
H 2 CO2
Bicarbonate exchange outside with Chloride ion by another pump
Proton secrete into lumen by H+
The chloride ion directly s K+
proton pump exchange of
ecrete into lumen potassium ion PP
H+
Cl -
Poton and chloride combines HCl
and produce HCl acid
Molecular mechanism
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.
Process of bioactivation
Step 1: Two nitrogen of the two ring of Pantoprazole are attacked by the proton.
2H+
Pantoprazole Protonated Pantoprazole
Molecular mechanism
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.
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).
-H +
-SH -SHSulfenamide(active drug)
-H 20
Molecular mechanism
◾How Acid secretion inhibited by pantoprazole
Pantoprazole enters into gastric parietal cell
- Inactive
Pantoprazole
Convert into active metabolite (Sulfenamide)
Sulfenamide interact with proton pump
Sulfenamide bind to proton pump at thial group Active drug
Proton pump cant pass proton to the lumen
HCl formation inhibited in Gastric environment
Molecular mechanism
◾How pantoprazole reacts with H+/K+ ATPase enzyme
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.
Proton pump
Cysteine
S
Sulfenamide H+/K+ ATPase(proton pump)
Sulfenamide – proton pump complex
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 can be used in the treatment of dyspepsia.
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.
Indications
Gastric Ulcer
Gastro esophagus
reflux disorder
Helicobacter-
Pantoprazole
pylori eradication
Zollinger ellison
syndrome
With NSAIDs
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
Pantoprazole CYP2C19 Inhibited CYP2C19
Reduced
Nelfinavir Inhibited CYP2C19 Active M8 metabolite Nelfinavir effect
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.
Pharmacokinetics(ADME)
Absorption
Absorption
Bioavailability: 77% (PO; neither food nor
antacid alters bioavailability) Distribution
Onset (PO PUD): 24 hr (initial response)
Protein bound: 98%
Duration (PO at steady state): 7 days (PUD)
Vd: 11-24 L
Peak plasma time: 2.8 hr (PO); at end of
infusion
Metabolism
Excretion
Metabolized extensively by hepatic P450
Half-life: 1 hr; increased to 3.5-10 hr with enzyme CYP2C19.
CYP2C19 deficiency Plasma concentration can increase by
Dialyzable: No 5-fold or more in comparison with that
Renal clearance: 0.1 L/hr/kg found in persons who have the enzyme.
Total body clearance: 7.6-14 L/hr Metabolites: Desmethylpantoprazole sulfa
Excretion: Urine (71%); feces (18%) te conjugate (activity unknown)
Metabolism
PPIs are enzymatically cleared in
the liver by demethylation reaction CYP2C19 Pantoprazole CYP3A4
primarily by the cytochrome P450 2C19 CYP3A4
(CYP2C19) enzyme, and to a lesser
extent by CYP3A4(oxidation).
Pantoprazole
Metabolites: 5-hydroxy sulfone Pantoprazol
5-hydroxy pantoprazole,Pantoprazole pantoprazole sulfide
sulphate, pantoprazole sulfone, Sulfo-
pantoprazole sulphate sulfone, Pantoprazole
transferase Pantoprazole
pantoprazole sulphide,pantoprazole sulphate
sulphate sulphide. sulphate sulfide (M3)
Pantoprazole CYP3A4 sulfone
sulphate
It is documented that CYP2C19 is (M2)
responsible for > 80% of the metabolism CYP3A4
of pantoprazole metabolism.
Dose,Dosage form and Strength
Indications Dose(Tabletl Time Dose (Iv injection) Time
For 4 weeks / 8 weeks
GaStric Ulcer 40 mg(Daily morning) 40mg once daily For 7-10 days
(if not healed)
20-40 mg For 4 weeks /8 weeks
GERD 40mg once daily For 7-10 days
(daily morning) (if not healed)
Zollinger ellison 80 mg daily 80 mg every 12 hours
Variable Variable
syndrome (adjusted) (Variable)
According to
Prophylaxis for NSAID 20 mg daily 80mg every 12 hours For 24 hours
NSAID
40 mg twice daily
According to
H-pylori ulcer associated with - -
antimicrobials
antimicrobials
Oral suspension Powder for injection Tablet(delayed-release) Tablet(Immediate release)
•40mg/packet •40mg/vial •20mg / 40mg •40mg
Side effects
Main side effects of Pantoprazole is
nausea,vomiting(4%), Headache(12%) Nausea
Diarrhoea(9%), dizziness(3%),
Allergic
abdominal pain(6%), joint pain(3%) reaction
Vomiting
Long term uses (over 3 years) can
cause vit-B12 deficiency(Numbness,
weakness) and also has probability Vit-B12 Side
Headache
of bone fracture.
deficiency
effects
Diarrhoea Abdom-in
al pain
Bone
fracture
Abdominal pain Headache
Precaution and warnings!
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.
Contraindication
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
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
