Some drugs are absorbed by lipid diffusion, which is a passive movement across cell

membranes that is driven by a concentration gradient; drug must be soluble in lipid.

Features of a drug affecting absorption: aqueous solubility (drug must be in solution) and
lipid solubility (to cross cell membranes).

 Drugs can be given to act systemically or locally; local act where they ae given/
systemically enter the blood stream (can go anywhere).
 Oral administration is the most common means of administering a drug because it is
convenient for patients.
 Drugs that are given orally are subject to first pass hepatic metabolism which can reduce
the bioavailability of the drug.
 Intravenous (IV) is special because the drug is placed directly into the bloodstream i.e. no
absorption required.
 Drugs are absorbed by crossing cell membranes through lipid diffusion, this requires the
drug to be partially soluble in lipid and the lipid solubility of many drugs is affected by
the pH of their surroundings.
 Bioavailability is a parameter used to define the proportion of a dose that enters the
systemic circulation and its affected by: how much drug is absorbed, and how much drug
undergoes first pass hepatic metabolism (oral administration).
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Steps of drug distribution:
- All drugs are diluted in the blood
- Only small (& not protein bound) drugs can escape vasculature into extracellular fluid
- Binding to cells/ uptake into cells; lipid solubility
Volume of body water in which a drug ‘appears’ to be dissolved in after it has distributed
throughout the body: Vd = X/C , X = amount in body, C= conc in plasma
Factors determining volume of distribution:
1. Drug binds to plasma proteins. C is big, Vd is small
2. Drug binds to tissues/ taken up by cells. C is small, Vd is large
For drugs that bind extensively to tissues Vd can be very much greater than volume of total
body water. Vd is useful for calculating how much drug will give a particular concentration
of drug in plasma; X = VdC where X is the dose of drug administered IV to give a desired
plasma concentration C.
Drugs are eliminated by excretion (kidney) and metabolism (liver); usually a combination of
both.
Drug can be water soluble and less lipid soluble so that it can be excreted. Excretion mainly
by kidneys, others are faeces, sweat, breathe, breast milk.
Renal Excretion; 3 key processes:
1. Glomerular filtration – drug out of blood, water soluble, not protein bound drug at
Bowman’s Capsules
2. Tubular secretion – drug out of blood – active carries – also protein bound drug – can be
competitively inhibited. E.g. Probenecid
- reduce renal excretion of acidic drug
- competes with other drugs for tubular secretion
- masks appearance of banned substances in urine
- not performance enhancing but banned in sport
3. Tubular reabsorption – puts drug back into blood – pH dependent
- passive movement across cell membrane (lipid soluble)
- pH dependent
- can be manipulated clinically in overdose; e.g. Aspirin overdose (acidic drug) – give
NaHCO3, make urine basic, increases amount of ionised aspirin, reduced
reabsorption, increase excretion
Renal Clearance; volume of plasma from which a drug is completely removed by kidneys
per unit time: CL renal = GF + TS – TR (Unit = ml/min).

Metabolism - biotransformation (chemical modification), involves chemical change to drug,

occurs in most tissue but MAINLY in liver, enzyme-catalysed reactions:
- Phase I – create functional group to drug
- Phase II – attach water soluble molecule to a drug
- Increased water solubility to facilitate excretion
Phase I; creates a chemical functional group on drug i.e. OH, NH2, SH, COOH | Cytochrome
P450: superfamily of enzymes, responsible for Phase I drug metabolism reactions, action can
be inhibited or enhanced by:
- drugs – leading to drug-drug interactions e.g. Antibiotics, contraceptive pill
- genetic variability – idiosyncratic responses e.g. Codeine
Idiosyncratic Effects:
- Infrequent
- Qualitatively abnormal response: dose dependent
- Genetically determined: due to alternation in metabolism
Phase II; conjugation of a water-soluble molecule to the functional group on drug
- e.g. Glutathione conjugation: in blood cells, major detoxification process
- e.g. Glucuronidation: codeine ------------------> morphine

 Vd quantitates how a drug spreads through the body [Vd = X/C]; if small the drug is in
the plasma/if large the drug is in the tissues; can be larger than total body water. If you
rearrange Vd it tells you the dose of drug you need to give a particular concentration [X =
VdC]
 Kidneys are mine site of drug excretion: 1. Glomerular filtration (drug out), 2. Tubular
secretion (drug out), 3. Tubular reabsorption (drug back in)
 Liver main site of drug metabolism: metabolism can affect pharmacological activity
 There are two types of metabolism: phase 1 creates a functional group on the drug, phase
2 attaches a water-soluble molecule on the drug
 The end effect of drug metabolism is to yield water-soluble metabolites that cannot be
readily reabsorbed, and therefore are excreted, i.e. metabolism and excretion work in
concert to bring about the elimination of a drug.
 Drugs are eliminated by processes that typically are dependent on the concentration of
drug in the blood, hence drugs have a half life which quantifies their persistence on the
bloodstream.
 Drugs given by a bolus IV curve will display an exponential decay curve when
concentration of drug in blood is plotted against time.
 Drugs given by an oral dose display a complex concentration vs time profile, reflecting
the changing rates of the drug in and out of the blood.