ADMET-summary
Camélia Hamidi Vrije University (Drug Discovery Sciences)
,Lecture 1
What routes can be used to administer drugs?
Route Amount/information Absorption/used Used for
on
IV intravenous Drugs are delivered Highly perfused Only aqueous solutions
rapidly, 100% organs (liver, Chemotherapeutics,
bioavailability kidney, heart lungs) antibiotics, pain relief
Injected directly into the are subject to high medicine (morphine)
bloodstream as a bolus concentrations in a
(rapid) or by infusion short time
(continuously) (IV)
IM intramuscular Different muscles have Upper part of arm Some antibiotics
different blood supply (2 mL); fast Vaccines
Difference in adipose absorption Some pain relief
young people and older Gluteus muscle (7- medicine (morphine
Parental route (Avoiding GIT)
people 8 mL); slower sometimes)
absorption because
of adipose tissue
SC subcutaneous Under the skin, into Slower absorption Insulin, Heparin,
adipose layer beneath than IM Biological (monoclonal
dermis Mainly absorbed antibodies)
Usually arm, thigh, via passive
abdomen (small volumes diffusion
max. 2 mL (<than IM))
Intraperitoneal Injection within peritoneal(abdominal) cavity (IP)
Epidural Injected into epidural space just inside the bone of lower vertebrae
transdermal (patch) Applied as a patch or other device and
transported through the skin (SC)
respiratory (asthma) and nasal Intranasal: Sprayed into the nose
Special cases: Intracardiac, intraspinal…
Oral Swallowed by mouth (PO)
Systemic/Enteral route (GIT)
• Buccal: Tablet held inside mouth between
cheek and gum
• Sublingual: Tablet under the tongue
Rectal/ Suppository Placed in the rectum
Camélia Hamidi Vrije University (Drug Discovery Sciences)
, Topical Applied as a solution or suspension on the skin
Primarily local effects
Ocular and optic Applied on the eyes
Vaginal Applied or inserted into the vagina
Respiratory and nasal Sprayed into the nose, for the nose or used for the
longs (only local)
Epidural Injected into epidural space just inside the bone of
other
lower vertebrae
GIT
• Oral is considered first choice and is the preferred route
• Absorption is dependent of the physiological state of the GIT and the physicochemical properties
• Secretion, digestion and absorption in GIT
• Varies from 0.4 – 5 days
• Different pH in each section
• Different types of digestion enzymes
• Variation in mucus composition (slijm)
Camélia Hamidi Vrije University (Drug Discovery Sciences)
, Small intestine
• pH is higher than in stomach (pH 1.4-2.1 (fasted) and 3-7 (fed) transit time: 0,5-1 hours)
• transit time: time available for absorption
Duodenum Jejunum Ileum
• pH (fasted) 4.4-6.6 • pH (fasted) 4.4-6.6 • pH (fasted) 6.8-8.0
• pH (fed) 5.2-6.2 • pH (fed) 5.2-6.2 • pH (fed) 6.8-8.0
transit time: 2-4 hours
Majority of pancreas enzymes added:
• proteases (trypsin, amylase, lipase)
• Hydrolysis of drugs
Pro-drugs designed to take advantage of hydrolysis
• First site metabolism: presence of CYP3A4 and others
• Solubility is enhanced by bile acids (released by gallbladder upon uptake of fatty food)
Drug absorption in GIT:
Trans diffusion Requires drug in solution, solubility, permeability
Paracellular passive diffusion Requires drug in solution, solubility, permeability
Endocytosis Solubility, permeability
Solubility: dependent on solvent, temperature, pH and more
Permeability: (P, cm/s) depended on whether passive, active or combination
• Lipophilic drugs have low aqueous solubility but high membrane permeability
• Ionized drugs usually more soluble in water, non-ionized easier by passive diffusion
• pH in small intestine 5-8, weak bases are absorbed more easily (predominance in non-ionized
form), acids likely ionized.
Which physiological barriers does the drug encounter during absorption?
GIT drug barriers
L-ADME (liberation)
• To overcome biological barriers, drug is released from carrier to free form
• Some dosage already has drug in solution
• Absorption depends on:
o Physicochemical properties, anatomical and physiological properties of the site of
absorption and administration environment (chapter 12)
Small intestine: has small circular folds/ large intestine: semilunar folds (Haustra)
• Key to absorption: large surface area (5 meter), mucosal folds, intestinal villi, microvilli on apical
surface cells
• Main cells involved with absorption: Enterocytes: lifespan of 4 days
• Mucus producing cells: Goblet cells
property description
Dissolution rate Rate of transfer of the compound from the surface to the aqueous solution
Solubility Maximum concentration that can be reached
Permeability Movement from aqueous solution through lipid membrane to aqueous solution on
the other side
Chemical instability Reaction of compound as a result of an environmental condition
Hydrolyzing enzymes Naturally occurring enzymes that catalyze hydrolysis of food and some drugs
Camélia Hamidi Vrije University (Drug Discovery Sciences)
Camélia Hamidi Vrije University (Drug Discovery Sciences)
,Lecture 1
What routes can be used to administer drugs?
Route Amount/information Absorption/used Used for
on
IV intravenous Drugs are delivered Highly perfused Only aqueous solutions
rapidly, 100% organs (liver, Chemotherapeutics,
bioavailability kidney, heart lungs) antibiotics, pain relief
Injected directly into the are subject to high medicine (morphine)
bloodstream as a bolus concentrations in a
(rapid) or by infusion short time
(continuously) (IV)
IM intramuscular Different muscles have Upper part of arm Some antibiotics
different blood supply (2 mL); fast Vaccines
Difference in adipose absorption Some pain relief
young people and older Gluteus muscle (7- medicine (morphine
Parental route (Avoiding GIT)
people 8 mL); slower sometimes)
absorption because
of adipose tissue
SC subcutaneous Under the skin, into Slower absorption Insulin, Heparin,
adipose layer beneath than IM Biological (monoclonal
dermis Mainly absorbed antibodies)
Usually arm, thigh, via passive
abdomen (small volumes diffusion
max. 2 mL (<than IM))
Intraperitoneal Injection within peritoneal(abdominal) cavity (IP)
Epidural Injected into epidural space just inside the bone of lower vertebrae
transdermal (patch) Applied as a patch or other device and
transported through the skin (SC)
respiratory (asthma) and nasal Intranasal: Sprayed into the nose
Special cases: Intracardiac, intraspinal…
Oral Swallowed by mouth (PO)
Systemic/Enteral route (GIT)
• Buccal: Tablet held inside mouth between
cheek and gum
• Sublingual: Tablet under the tongue
Rectal/ Suppository Placed in the rectum
Camélia Hamidi Vrije University (Drug Discovery Sciences)
, Topical Applied as a solution or suspension on the skin
Primarily local effects
Ocular and optic Applied on the eyes
Vaginal Applied or inserted into the vagina
Respiratory and nasal Sprayed into the nose, for the nose or used for the
longs (only local)
Epidural Injected into epidural space just inside the bone of
other
lower vertebrae
GIT
• Oral is considered first choice and is the preferred route
• Absorption is dependent of the physiological state of the GIT and the physicochemical properties
• Secretion, digestion and absorption in GIT
• Varies from 0.4 – 5 days
• Different pH in each section
• Different types of digestion enzymes
• Variation in mucus composition (slijm)
Camélia Hamidi Vrije University (Drug Discovery Sciences)
, Small intestine
• pH is higher than in stomach (pH 1.4-2.1 (fasted) and 3-7 (fed) transit time: 0,5-1 hours)
• transit time: time available for absorption
Duodenum Jejunum Ileum
• pH (fasted) 4.4-6.6 • pH (fasted) 4.4-6.6 • pH (fasted) 6.8-8.0
• pH (fed) 5.2-6.2 • pH (fed) 5.2-6.2 • pH (fed) 6.8-8.0
transit time: 2-4 hours
Majority of pancreas enzymes added:
• proteases (trypsin, amylase, lipase)
• Hydrolysis of drugs
Pro-drugs designed to take advantage of hydrolysis
• First site metabolism: presence of CYP3A4 and others
• Solubility is enhanced by bile acids (released by gallbladder upon uptake of fatty food)
Drug absorption in GIT:
Trans diffusion Requires drug in solution, solubility, permeability
Paracellular passive diffusion Requires drug in solution, solubility, permeability
Endocytosis Solubility, permeability
Solubility: dependent on solvent, temperature, pH and more
Permeability: (P, cm/s) depended on whether passive, active or combination
• Lipophilic drugs have low aqueous solubility but high membrane permeability
• Ionized drugs usually more soluble in water, non-ionized easier by passive diffusion
• pH in small intestine 5-8, weak bases are absorbed more easily (predominance in non-ionized
form), acids likely ionized.
Which physiological barriers does the drug encounter during absorption?
GIT drug barriers
L-ADME (liberation)
• To overcome biological barriers, drug is released from carrier to free form
• Some dosage already has drug in solution
• Absorption depends on:
o Physicochemical properties, anatomical and physiological properties of the site of
absorption and administration environment (chapter 12)
Small intestine: has small circular folds/ large intestine: semilunar folds (Haustra)
• Key to absorption: large surface area (5 meter), mucosal folds, intestinal villi, microvilli on apical
surface cells
• Main cells involved with absorption: Enterocytes: lifespan of 4 days
• Mucus producing cells: Goblet cells
property description
Dissolution rate Rate of transfer of the compound from the surface to the aqueous solution
Solubility Maximum concentration that can be reached
Permeability Movement from aqueous solution through lipid membrane to aqueous solution on
the other side
Chemical instability Reaction of compound as a result of an environmental condition
Hydrolyzing enzymes Naturally occurring enzymes that catalyze hydrolysis of food and some drugs
Camélia Hamidi Vrije University (Drug Discovery Sciences)
