PHARMACOKINETICS
OF
CIMETIDINE
PREPARED BY
‫حيدر‬ ‫عبدهللا‬ ‫امين‬ ‫بشبر‬
‫إشراف‬ ‫تحت‬
‫الفاضل‬ ‫الدكتور‬
:
‫محمود‬
‫البريهي‬

CIMETIDINE
Table Of
Content
Background
Structure
Indication
Contraindications
& Blackbox
Warnings
Pharmacodynamics
Mechanism of action
Pharmacokinetics
Drug Interactions
Calculations for
the
parameters

Background
SUMMARY
Cimetidine is a histamine H2 receptor antagonist used to
manage GERD, peptic ulcer disease, and indigestion.
BRAND NAMES
Good Sense Heartburn Relief, Tagamet
GENERIC NAMES
Cimetidine
BACKGROUND:
important hydrogen histamine receptor. It is widely employed in
medicine due to its protective action in stomach ulcerations.
Cimetidine is highly stable, thus in 24 h about 50 to 80% of the
delivered dose is excreted unaltered.
A recent study investigated changes in pH and
levels of histamine over the oxyntic glands of guinea pig stomach.
Researchers observed decrease in pH, which
was due to acid secretion. Simultaneous measurements
were carried out during the cimetidine pharmacological
treatment. A sharp increase in histamine and a decrease in
acid secretion were observed. Cimetidine accumulation is
associated
to the risk of prostate cancer, due to the reduction
in zinc levels, which are essential to the regulation of cell
cycles and apoptosis induction

Structure
DRUG NAME INFO
Drug Name Info US Trade Names
Tagamet Tagamet HB Class
Gastric Acid Secretion Inhibitor Histamine H2 Antagonis
Regulatory Status RX/OTC Generic
Availability Yes
Structure
INN name: Cimetidine,
Chemical name:
N00cyano-N-methyl-N0 -[2([(5-methyl-1H-imidazol-
4yl)methyl]thio)ethyl] guanidine.
WEIGHT
Average: 252.339
Monoisotopic: 252.115715232

CHEMICAL PROPERTIES OF CIMETIDINE
Chemical formula
C10H16N6S
Molecular weight 252.339 g/mole
PH :
basic drug
Solubility:
Hydrophobic
8.0-9.5
Solubility: Soluble (1.14%) in water at
37°C;soluble in ethanol; very slightly
soluble in chloroform; insoluble in
diethyl ether

Clinical use of Cimetidine
FDA-Labeled Indications
Erosive esophagitis
Gastric ulcer,Active,
Systemic mast cell disease
Erosive esophagitis
Gastric ulcer,Active
Zollinger-Ellison
syndrome
Ulcer of duodenum
Active Ulcer of duodenum Maintenance
Zollinger-Ellison syndrome
Systemic mast
cell disease

Clinical use of Cimetidine
Non-FDA Labeled Indications
Aspiration pneumonitis; Prophylaxis
Contrast media adverse reaction
Gastric ulcer, Maintenance
Gastric ulcer,
Maintenance
Measurement of renal
clearance
Verruca vulgaris
Measurement of renal clearance
Stress ulcer
Verruca vulgaris
Aspiration
pneumonitis;

Dosage
of
Cimetidine
Injectable solution
150mg/mL
Oral solution
300mg/5mL
Tablet
200mg , 300mg , 400mg
(Rx)600mg (Rx) 800mg (Rx)

Contraindication of
Cimetidine
Hypersensitivity to
cimetidine or other
H2 receptor
antagonists

Protein
binding,
13% to 26%
Vd: 1 L/kg
Pharmacokinetics
of
Cimetidine
30 L/hr to 48 L/hr
ABSORPTION
Tmax, Oral: 45 to 90
minutes
Bioavailability, Oral:
70% to 76%
DISTRIBUTION
METABOLISM
Hepatic,
approximately 50%
Cimetidine
sulfoxide (major):
inactive
EXCRETION
Renal excretion: 48%
Renal clearance:
13.8 L/hr to 30 L/hr
Dialyzable: yes
(hemodialysis) , 20.4
mL/min to 37.4 mL/min;
Eliminatio
n Half Life
2 hours
ELIMINATION HALF LIFE
yes (peritoneal dialysis),
4.2 mL/min to 5 mL/min
Total body clearance:

Cimetidine is a histamine H -receptor antagonist. It reduces
basal and nocturnal gastric acid secretion and a reduction
in gastric volume, acidity, and amount of gastric acid
released in response to stimuli including food, caffeine,
insulin, betazole, or pentagastrin. It is used to treat
gastrointestinal disorders such as gastric or duodenal ulcer,
gastroesophageal reflux disease, and pathological
hypersecretory conditions. Cimetidine inhibits many of the
isoenzymes of the hepatic CYP450 enzyme system. Other
actions of Cimetidine include an increase in gastric
bacterial flora such as nitrate-reducing organisms.
Pharmacodynamics

M echanism
of action
Cimetidine
receptor
binds
to
located
an
H
-
on
the
basolateral
membrane
of
the
gastric
parietal
cell,
blocking
histamine
effects.
This
competitive
inhibition
results
in reduced gastric acid
secretion and a reduction in
gastric volume and acidity.
Cimetidine is a H2 blocker that
acts by inhibiting histamine
action at the histamine H2
receptors of the parietal cells.
Cimetidine inhibits both
daytime and nocturnal basal
gastric acid secretion, as well as
gastric acid secretion
stimulated by food, histamine,
pentagastrin, caffeine, and
insulin.

Pharmacokinetics
parameter of Cimetidi
Therapeutic Plasma
concentration range
(0.64–1.64 μg/ml).
Bioavailability (65%).
Volume Distribution VD
(1
L/kg) ×70 =70 L for
ideal body weight 70kg.
T1/2 (2hur).
1)Cp target =0.6 ng/ml +1.64 ng/ml =0.98/2=
0.5 ng/ml ×0.00l mg/L =0.0005 mg/L
2) K =
0.693 /t1
/2 =0.693 /2 =0.34
3) Cl =k ×vd =0.34 ×70 =24.2 L/hrs
7) AUC =dose/CL =400 /24.2 L/hr =
1
6.5 mg.h/L
4) LD =Cp ×vd /F =0.0005 mg/L ×70L /0.65
=0.05 mg
6) T1
/2 =0.693 ×Vd /Cl =0.693 ×70/24.2 L/hr
=2 hr
8) TW=C max/C min =
1
.64 ng/ml /0.6 ng/ml
=2.7
9) DI max= 1.44× t1/2 ×ln ( TW) =1.44 ×2 ×ln(2.7)
=2.86 hr

DRUG
Abacavir
Abemaciclib
Abrocitinib
Acalabrutinib
Acamprosate
Acebutolol
Aceclofenac
Acemetacin
Acenocoumarol
Acetaminophen
INTERACTION INTEGRATE DRUG-DRUG INTERACTIONS IN YOUR SOFTWARE
Cimetidine may decrease the excretion rate of Abacavir which could result in a higher serum level.
The metabolism of Abemaciclib can be decreased when combined with Cimetidine.
The metabolism of Abrocitinib can be decreased when combined with Cimetidine.
The metabolism of Acalabrutinib can be decreased when combined with Cimetidine.
The excretion of Acamprosate can be decreased when combined with Cimetidine.
The metabolism of Acebutolol can be decreased when combined with Cimetidine.
Aceclofenac may decrease the excretion rate of Cimetidine which could result in a higher serum lev
Acemetacin may decrease the excretion rate of Cimetidine which could result in a higher serum leve
The serum concentration of Acenocoumarol can be increased when it is combined with Cimetidine.
The metabolism of Acetaminophen can be decreased when combined with Cimetidine.
Drug - Drug Interactions

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Thank
You..
Clinica l-pha rma cokinetics-
pharmacy- handbook
Shargel bioph arm
Medscape
Reference
4 Micromedex