Drug Absorption Total Session Time: 120 minutes
Session 1: Drug Absorption
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Describe absorption
Describe factors affecting/determining absorption
Differentiate between Absolute and relative bioavailability
Calculate bioavailability
Explain clinical application of bioavailability
Resources Needed:
Flip charts, marker pens, and masking tape
Black/white board and chalk/whiteboard markers
LCD projector and computer
SESSION OVERVIEW
Step
Time
Activity/
Content
Step
Time
Activity/
Content
Step
Time
Method
Content
Method
Method
1
1
05 minutes
05 minutes
Presentation
Introduction, Learning Tasks
Introduction, Learning Tasks
2
2
10 minutes
10 minutes
Presentation/
Definition of Absorption
Definition of Absorption
2
2
10 minutes
10 minutes
Buzzing
Definition of Absorption
Definition of Absorption
Buzzing
Presentation/
3
3
45 minutes
45 minutes
Small Group
Factors Affecting Absorption
Factors Affecting Absorption
Discussion
4
4
20 minutes
20 minutes
Presentation
Absolute and Relative Bioavailability
Absolute and Relative Bioavailability
5
5
20 minutes
20 minutes
Presentation/
Calculation of Bioavailability
Calculation of Bioavailability
5
5
20 minutes
20 minutes
Brainstorming
Calculation of Bioavailability
Calculation of Bioavailability
Brainstorming
6
6
10minutes
10minutes
Presentation
Clinical Application of Bioavailability
Clinical Application of Bioavailability
7
7
05 minutes
05 minutes
Presentation
Key Points
Key Points
8
8
05 minutes
05 minutes
Presentation
Evaluation
Evaluation
PST 05104 Pharmacology & Therapeutics NTA Level 5 Semester 1 Facilitator Guide
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Description of Absorption (10 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
What is absorption?
ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board
CLARIFY and SUMMARIZE by using the content below
Absorption follows administration and is the process by which a drug is made available for use in the body.
It is the transfer of a drug from its site of administration to the
Blood stream.
It occurs after dissolution of a solid form of the drug or after the administration of a liquid or parenteral drug.
In this process the drug particles within the gastrointestinal tract are moved into the body fluids.
pinocytosis.
In active absorption a carrier molecule such as a protein or enzyme actively moves the drug across the membrane.
Passive absorption occurs by diffusion (movement from a higher concentration to a lower concentration).
In pinocytosis cells engulf the drug particle causing movement across the cell
STEP 3: Describe Factors Affecting Absorption (45 Minutes)
Activity: Small Group Discussion ( 20 minutes)
DIVIDE students into small manageable groups ASK students to discuss on the following question
What are factors affecting drug absorption? ALLOW students to discuss for 15 minutes
ALLOW few groups to present and the rest to add points not mentioned
CLARIFY and SUMMARIZE by using the contents below:
PST 05104 Pharmacology & Therapeutics 2 NTA Level 5 Semester 1 Facilitator Guide
Absorption
Absorption is the movement of a drug from its site of administration into the blood.
Most drugs are absorbed by passive absorption but some drugs need carrier mediated transport. Small molecules diffuse more rapidly than large molecules.
Lipid soluble non – ionized drugs are absorbed faster.
Factors determining absorption include;
route of administration,
Blood flow to the absorption site
Surface area available for drug absorption
GI motility
Physiochemical properties of drugs
Particle size of the formulation
Route of administration
Drugs are most rapidly absorbed when given by the intravenous route, followed by the intramuscular route, the subcutaneous route, and lastly, the oral route.
Typically, about 75% of a drug given orally is absorbed in 1-3 h, but numerous factors alter this, some physiological and some to do with the formulation of the drug.
The main factors are:
o gastrointestinal motility o splanchnic blood flow
o particle size and formulation o Physicochemical factors.
Blood flows faster through the deltoid muscle (in the upper arm) than through the gluteal muscle (in the buttocks).
o The gluteal muscle, however, can accommodate a larger volume of drug than the
deltoid muscle
Fig 1.1 Main routes of drug administration
PST 05104 Pharmacology & Therapeutics 3 NTA Level 5 Semester 1 Facilitator Guide
Blood flow to the absorption site
o Blood flow to the intestine is much greater than the flow to the stomach resulting to a favored absorption from the intestine over that from stomach.
Total surface area available for absorption
o Absorption of a drug across the GI tract is much efficient in the small intestine than the stomach due to a higher surface area resulting from presence of microvilli:
o Other bodily conditions such as the development of lipodystrophy (atrophy of the subcutaneous tissue) from repeated subcutaneous injections inhibit absorption of a drug given in the site of lipodystrophy.
Enzyme activity
o Drugs such as insulin and other proteins may be degraded by gastric enzyme resulting to poor absorption.
o The presence of food in the stomach both dilutes the drug and slows gastric emptying thus taking a drug together with food results to a generally slow absorption.
GI tract motility
Gastrointestinal motility has a large effect. Many disorders (e.g. migraine, diabetic neuropathy) cause gastric stasis and slow drug absorption.
Drug treatment can also affect motility, either reducing (e.g. drugs that block muscarinic receptors) or increasing it (e.g. metoclopramide, which is used in migraine to facilitate absorption of analgesic).
Excessively rapid movement of gut contents can impair absorption.
A drug taken after a meal is often more slowly absorbed because its progress to the small intestine is delayed.
There are exceptions, however, and several drugs (e.g. propranolol) reach a higher plasma concentration if they are taken after a meal, probably because food increases splanchnic blood flow.
Physicochemical factors
Solubility:
o Some drugs are more soluble and thus are absorbed more rapidly than others
o Non-polar molecules (in which electrons are uniformly distributed) dissolve freely in membrane lipids, and consequently diffuse readily across cell membranes.
o Consequently, there is a close correlation between lipid solubility and the permeability of the cell membrane to different substances.
o For this reason, lipid solubility is one of the most important determinants of the pharmacokinetic characteristics of a drug, and many properties-such as rate of absorption from the gut, penetration into different tissues and the extent of renal elimination-can be predicted from knowledge of a drug's lipid solubility.
pH and ionization.
PST 05104 Pharmacology & Therapeutics 4 NTA Level 5 Semester 1 Facilitator Guide
For most drugs the mechanism of absorption is the same as for other epithelial barriers, namely passive transfer at a rate determined by the ionisation and lipid solubility of the drug molecules.
Figure 1.2 below shows the absorption of various weak acids and bases as a function
of pKa.
As expected, strong bases of pKa 10 or higher are poorly absorbed, as are strong acids of pKa less than 3, because they are fully ionised
Fig 1.2 Absorption of drugs from the intestine, as a function of pKa, for acids and bases. Weak acids and bases are well absorbed; strong acids and bases are poorly absorbed. (Redrawn from Schanker L S et al. 1957 J Pharmacol 120: 528.)
Drug interaction
o Some drug interactions affect drug absorption. For example Tetracycline binds strongly to Ca2+, and calcium-rich foods (especially milk) prevent its absorption.
o Bile acid-binding resins such as colestyramine (used to treat certain forms of hyper-cholesterolaemia) bind several drugs, for example warfarin and thyroxine.
Tablets from different manufacturers may result into different plasma concentrations even though the active ingredient content is the same because of different particle size.
Therapeutic drugs are formulated pharmaceutically to produce desired absorption characteristics.
Capsules may be designed to remain intact for some hours after ingestion in order to delay absorption, or tablets may have a resistant coating to give the same effect.
In some cases, a mixture of slow- and fast-release particles is included in a capsule to produce rapid but sustained absorption.
PST 05104 Pharmacology & Therapeutics 5 NTA Level 5 Semester 1 Facilitator Guide
Fig 1.3 Variation in oral absorption among different formulations of digoxin.
Rang and Dale pharmacology seventh
edition
The four curves show the mean plasma concentrations attained for the four preparations, each of which was given on separate occasions to four subjects. The large variation has caused the formulation of digoxin tablets to be standardised since this study was published. (From Lindenbaum J et al. 1971 N Engl J Med 285: 1344.)
STEP 4: Absolute and Relative Bioavailability (20minutes)
The term bioavailability is used to indicate the proportion of drug that passes into the systemic circulation after oral administration, taking into account both absorption and local metabolic degradation.
Drugs must enter the circulation if they are to exert a systemic effect.
Unless administered intravenously, most drugs are absorbed incompletely
There are three reasons for this:
o the drug is inactivated within the gut lumen by gastric acid, digestive enzymes or bacteria;
o absorption is incomplete;
o presystemic (‗first-pass‘) metabolism occurs in the gut wall and liver.
Together, these processes explain why the bioavailability of an orally administered drug is typically less than 100%.
Bioavailability of a drug formulation can be measured experimentally by measuring concentration vs. time curves following administration of the preparation via its intended route (e.g. orally) and of the same dose given intravenously
PST 05104 Pharmacology & Therapeutics 6 NTA Level 5 Semester 1 Facilitator Guide
Fig 1.4 Blood concentration-time curves, illustrating how changes in the rate of absorption and extent of bioavailability caninfluence both the duration of action and the effectiveness of the same total dose of a drug administered
Absolute Bioavailability
o Is the fraction of drug that reaches systemic circulation. I.V. is used as reference Relative Bioavailability
o The amount of drug that reaches the system compared to the amount from another standard formulation
Table 1.1 Routes of administration, bioavailability, and general characteristics.
Betram G Katzung basic and clinical
pharmacology twelveth edition
PST 05104 Pharmacology & Therapeutics 7 NTA Level 5 Semester 1 Facilitator Guide
STEP 5: Calculation of Bioavailability (20 Minute)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What is the bioavailability of paracetamol when 100mg is taken orally and 67mg of
the drug reaches systemic circulation?
ALLOW few students to respond?
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
The bioavailability of paracetamol is 0.67
STEP 6: Clinical Application of Bioavailability (10minutes)
Absolute Bioavailability is important in determining the amount of drug which will reach systemic circulation hence available for distribution and consequently for action
Difference in bioavailability between brands may lead to toxicities or reduced potency. o For example,
Differences in bioavailability did account for an epidemic of phenytoin intoxication in Australia in 1968–69.
Affected patients were found to be taking one brand of phenytoin in which the excipient had been changed from calcium sulphate to lactose, increasing phenytoin bioavailability and thereby precipitating toxicity.
o Furthermore, an apparently minor change in the manufacturing process of digoxin in the UK resulted in reduced potency due to poor bioavailability.
Therefore Prescribers need to be confident that different preparations (brand named or generic) are sufficiently similar for their substitution to be unlikely to lead to clinically important alterations in therapeutic outcome
PST 05104 Pharmacology & Therapeutics 8 NTA Level 5 Semester 1 Facilitator Guide
STEP 7: Key Points (5 minutes)
Absorption occurs through passive diffusion or active transport
Zero per cent bioavailability implies that no drug enters the systemic circulation, whereas 100% bioavailability means that all of the dose is absorbed into the systemic circulation.
Bioavailability may vary not only between different drugs and different pharmaceutical formulations of the same drug, but also from one individual to another,
STEP 8: Evaluation (5 minutes)
What is absorption?
What are the factors affecting absorption of drugs?
What is absolute bioavailability?
PST 05104 Pharmacology & Therapeutics 9 NTA Level 5 Semester 1 Facilitator Guide
References
Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.
Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.
Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:
Jaypee Brothers Medical P.
Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.
Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.
School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).
Dar es Salaam, ARDHI University press.
The Royal Pharmaceutical Society of Great Britain. (2007). Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.
The Royal Pharmaceutical Society of Great Britain. 2009. British National Formulary (59th ed). London, BMJ Group and RPS Publishing.
PST 05104 Pharmacology & Therapeutics 10 NTA Level 5 Semester 1 Facilitator Guide
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