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Glaxo Wellcome
Pharmacology Guide

In vivo pharmacology: definitions and calculations

Abbreviation for base (or biological) equivalent weight. Drug doses are usually expressed in terms of the weight of active substance (usually a base). When a drug salt (e.g. a hydrochloride) or a form which contains water of crystallisation is used, the BEW is the ratio which determines how much salt (or hydrated compound) has to be used to give the desired dose of active drug.

                     Mol. wt. of salt
      BEW =    ----------------------------
                 Mol. wt. of active moeity

Blind study
A study in which the experimenter is unaware of which test procedure the animal has received. Compare double-blind.

Blood-brain barrier
The endothelial cells of the capillaries of the brain and spinal cord are linked by tight junctions which prevent direct contact between plasma and cells of the central nervous system. Lipophilic drugs can diffuse across this barrier; some nutrients are actively transported across it. Other substances may have very poor access to the brain.

Confidence limits
A statistical measure of the reliability of biological data values. Usually, 95% confidence limits are quoted. These would enclose the true value in 95% of repeated experiments.

Crossover design
A test in which two drugs (or one drug and placebo) are compared. The patient or animal is started on one treatment, and then after a specified time changed to the other treatment.

Double-blind study
A clinical trial or experiment in which neither the investigators nor the patients know which treatment has been administered.

Dose of drug which produces 50% of its maximum response or effect. Alternatively, the dose which produces a pre-determined quantal (all-or-nothing) response in 50% of test subjects or preparations.

Equi-potent molar ratio (better expressed as equi-effective molar ratio). The molar ratio of doses of test and standard compound which produce a given level of response.

                ED50 of test compound
EPMR    =    -------------------------- 
                 ED50 of standard

where the ED50 values are expressed in moles/kg. EPMR values may also be quoted for experiments in vitro, when molar concentrations are used instead of doses. In either case, the lower the EPMR, the more potent the compound.

First-pass metabolism
Drugs which are absorbed from the gut travel directly to the liver where some are extensively metabolised before they can reach their intended site of action.

ID50 (also in vitro)
A dose which causes 50% of the maximum possible inhibition of a response for a given drug.

Latin square design
A randomisation schedule for drug tests in which each animal receives each treatment once, in a predetermined random sequence. Also used in randomising doses in some isolated tissue experiments. An example for four drugs (A,B,C,D) in a four-day study is shown below.

GIF version of table

Animal Drug on day number:
1 2 3 4
1 A B C D
2 C A D B
3 D C B A
4 B D A C

A dummy treatment in a clinical trial, designed to assess the extent to which factors other than the drug under test affect the outcome of the disease.

See (section 2).

Term used to represent various biological half-lives for a drug, including: (a) the kinetic or metabolic half-life, i.e. the time for the concentration of drug in plasma to decline to half its original level; (b) the half-life of the effect of a drug, i.e. the time necessary for the response to the drug to decline to half the original response.

Therapeutic index
(or therapeutic ratio). The ratio of the toxic dose of the drug to the dose which causes the desired therapeutic effect.

The solvent used to dissolve drugs: often water or isotonic (0.9%) saline solution. May itself be administered to some animals in a control experiment. See also placebo.


Forward Routes of administration
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