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Pharmacokinetics: Drug Absorption, and Factors affecting absorption

Learning Objectives:

At the end of the lecture, the student should be able to:

Describe pharmacokinetics.

Give the mechanisms of drug Absorption.

Discuss the various factors that affect absorption.

Explain what is bioavailability and give the factors affecting bioavailability.

Pharmacokinetics of drugs:

Are studies of:

Absorption

Distribution

Metabolism

Excretion of drugs.

Drug absorption:

Is the passage of drug through cell membranes to reach its site of action.

Mechanisms of drug absorption

1. Simple diffusion = passive diffusion.

2. Active transport.

3. Facilitated diffusion.

4. Pinocytosis (Endocytosis).

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pKa- pH= log protonated / non-protonated

PKa of the drug:

(Dissociation or ionization constant):

pH at which half of the substance is ionized & half is unionized.

pH of the medium:

Affects ionization of drugs.

Weak acids best absorbed in stomach.

Weak bases best absorbed in intestine.

Which one of the following drugs will be best absorbed in stomach (pH=3)?

Aspirin, pka=3.0

warfarin, pka=5.0

Arrange the following drugs in ascending order from least to greatest in rate of

absorption in small intestine (pH=7.8)?

Propranolol, pka= 9.4

Aspirin, pka=3.0

warfarin, pka=5.0.

Active Transport:

Relatively unusual.

Occurs against concentration

gradient.

Requires carrier and energy.

Specific

Saturable.

Iron absorption.

Uptake of levodopa by brain.

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Carrier-mediated Facilitated Diffusion

Occurs along concentration gradient.

Requires carriers

Selective.

Saturable.

No energy is required.

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Solubility

Drug pH

Concentration

Patient factors

Absorbing surface

Blood flow

Environmental pH

Disease states

Interactions with food, other drugs

Bioavailability:

Is the fraction of unchanged drug that enters systemic circulation

after administration and becomes available to produce action

I.V. provides 100% bioavailability.

Oral usually has less than I.V.

Bioavailability = AUC oral / AUC I.V 100

Factors Affecting Bioavailability:

Molecular weight of drug.

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Drug formulation (ease of dissolution).

(solution > suspension > capsule > tablet)

Drug solubility

Chemical instability in gastric pH (Penicillin

& insulin )

First pass metabolism reduces bioavailability

Blood flow to absorptive site

Greater blood flow increases bioavailability

Intestine has greater blood flow than stomach

Surface area available for absorption.

Intestinal microvilli increases it

Rate of gastric emptying

rapid gastric emptying, fast transit to intestine

pH of gut

Intestinal motility (Transit Time)

Diarrhea reduce absorption

Drug interactions

Food

slow gastric emptying

generally slow absorption

Tetracycline, Aspirin, Penicillin V

Thank You.