Immunoassay and Pharmacokinetics

Since its introduction, 30 years ago, immunoassay has spread widely into areas extending from biology to the environment. The pharmaceutical industry has benefited from this new analytical technique both in the development of medicines and in quality control during manufacture and drug monitoring.

The objective of pharmacokinetics is to study the fate of drugs in the body and thereby propose a rational administration for optimising therapeutic effect. These studies performed by administration of radio-labelled compounds in animals or by conventional analysis generally use techniques of a chroma-tographic type in which the limit of detection is rela-tively high (over 1ng/ml). Immunoassay on the other hand permits detection of plasma levels of less than 1 ng/ml. These results lead to a better definition of the pharmacokinetic characteristics, such as, for ex-ample, observation of a longer elimination phase, demonstration of an enterohepatic cycle or more accurate determination of bioavailability.

The example shown in the Figure illustrates this perfectly. A synthetic progestative administered orally in a dose of 5 mg cannot be detected 24 hours later by a liquid chromatography technique and ultraviolet detection, whereas the compound can be monitored for up to 5 days by enzyme immunoassay.

The specificity of immunoassay can be used for the estimation of metabolites and can provide informa-tion on their pharmacokinetics. This type of determi-nation can be stereospecific and thus permit the measurement of just one enantiomer, which is par-ticularly interesting when this is the only one with pharmacological activity. The last few years have seen the development of a new class of therapeutic agents consisting of pep-tides or recombinant proteins. These compounds are characterised by low dosage and measurement of their circulating blood-levels, which are often below 500 pg/ml, requires immunoassay techniques. Im-munoassays could in future permit by virtue of their rapidity of execution the use of a personalised dosage scheme for those compounds with a narrow therapeutic interval and a high inter-patient variation.

Immunoassay offers flexibility in its application to pharmacokinetics: smaller volumes of samples (less than 500 microlitres) are required, number of steps to realise the assay is limited and the determination is easy to perform. Immunoassay techniques are more-over very reliable and most of them show coefficients of repeatability or of reproducibility of less than 15% and thus meet the quality criteria demanded for the conduct of pharmacokinetic or bioequivalence stud-ies. E.E.

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