Pharmacokinetics: Basic Considerations

Pharmacokinetics: Basic Considerations

The duration of drug therapy ranges from a single dose of a drug taken for relieving an acute condition such as headache to drugs taken life-long for chronic conditions such as hypertension, diabetes, asthma or epilepsy. The frequency of administration of a drug in a particular dose is called as dosage regimen. Depending upon the therapeutic objective to be attained, the duration of drug therapy and the dosage regimen are decided.

Rational and optimal therapy with a drug depends upon –

1. Choice of a suitable drug, and

2. A balance between the therapeutic and the toxic effects.

Both, the therapeutic and the toxic effects, depend upon the concentration of drug at the site of action which is difficult to measure. However, it corresponds to a specific concentration of drug in plasma which can be measured with accuracy. The drug fails to elicit a therapeutic response when the concentration is below the effective level and precipitates adverse reactions when above the toxic level. The plasma drug concentration between these two limits is called as the therapeutic concentration range or therapeutic window (the ratio of maximum safe concentration to minimum effective concentration of the drug is called as the therapeutic index). Thus, in order to achieve therapeutic success, plasma concentration of the drug should be maintained within the therapeutic window. For this, knowledge is needed not only of the mechanisms of drug absorption, distribution, metabolism and excretion, but also of the kinetics of these processes i.e. pharmacokinetics. Pharmacokinetics is defined as the kinetics of drug absorption, distribution, metabolism and excretion (KADME) and their relationship with the pharmacological, therapeutic or toxicological response in man and animals. There are two aspects of pharmacokinetic studies –

1. Theoretical aspect – which involves development of pharmacokinetic models to predict drug disposition after its administration. Statistical methods are commonly applied to interpret data and assess various parameters.

2. Experimental aspect – which involves development of biological sampling techniques, analytical methods for measurement of drug (and metabolites) concentration in biological samples and data collection and evaluation.

Several relevant terms can now be defined –

^·            Clinical Pharmacokinetics is defined as the application of pharmacokinetic principles in the safe and effective management of individual patient.

^·            Population Pharmacokinetics is defined as the study of pharmacokinetic differences of drugs in various population groups.

^·            Toxicokinetics is defined as the application of pharmacokinetic principles to the design, conduct and interpretation of drug safety evaluation studies.