Intro to pharmacokinetics

Types of dug delivery

Direct to site

Indirect

Direct to site

• skin, eye, gut, lung

• More difficult for other sites but can be done

Indirect (drug delivery)

• via systemic circulation

• Introduces problems of loss or dilution of does

Routes of administration inhalation

• gases

• Volatiles

Oral

• tablets

• Capsules

• Solutions

• Buccaneers

Injection

Intravenous

Intramuscular

Subcutaneous

Intrathecal

Where are oral drugs absorbed ?

In the gastrointestinal tract

Where are transdermal drugs absorbed?

Across the skin

Hypodermic injections absorbed in

From injection site

Here in lung are drugs absorbed?

Alveolar surface

What surfaces must cross to enter blood?

• epidermal/ mucosal surfaces

What determines drug distribution?

• binding to plasma proteins

• Structure of vascular endothelium ‘

• Accumulation in tissue depots

Highly perfumed lean tissue group examples

Blood cells, heart, lung, Liver, kidney, glands, brain

Poorly -perfumed lean tissue group

Muscle, skin

Fat group

Adipose tissue , bone marrow

Negligible perfusion group

Teeth, hair, bone, tendon, cartilage

Two phases of metabolism

1. Redox rxns

2. Conjugation rxns to add bulky groups

Phase I

Cytochrome P450

Multiple isoforms

Multiple substrates

Redox rxns

Phase 2

UDP-glucuronyl transferases

Multiple isoforms

Multiple substrates

Conjugatiion

Key stages of excretion

• passive filtration

• Active secretion

• Reabsorption

Stages of renal clearance

1. Assume filtration in glomerulus

2. Active secretion in proximal tubule

3. Reabsorption in distal tubule

Passive filtration in glomerulus

Plasma forced from blood into Bowman’s capsule

Drug free in solution passively carried over into filtrate

Active secretion in proximal tubule

Transporter proteins extract drug from blood and drive into filtrate

Drug can be concentrated

What is sone because we can’t measure drug conc at target site

Assume direct correlation between plasma conc at target and drug effect

Quantification of absorption

Bioavailability (F)

Cmax, tmax

Quantification of distribution

Vol of distribution (Vd)

Quantification of Elimination

Half life (t1/2)

Clearance (CL)

Therapeutic window

• changing conc (hard to dose)

• Plasma conc range span from therapeutic effect and onset of side effects

Challenges with narrow therapeutic range

• difficult to use

• May require frequent therapeutic drug monitoring

When might r/s between plasma conc not hold

• effect is mediated through metabolite

• Effect is irreversible

• Kinetics in the target compartment is different from that in blood