Clinical application blood drug measurements

While the study of the absorption, disposition, metabolism, and excretion of drugs, and their therapeutic applications falls properly within the province of the clinical pharmacologist, it is upon the skills and knowledge of the clinical biochemist that accurate, and hence clinically meaningful, measurements of blood drug concentrations depend. The clinical biochemist must therefore be familiar not only with the methodology, but also with the value, and limitations, of such measurements. 

Measurement of a metabolite may be preferred when parent drug levels are too low to allow reliable analytical measurement in blood, plasma, or serum for an adequate length of time. The metabolite data obtained from these studies should be subject to a Cl approach for BE demonstration. If there is a clinical concern related to efficacy or safety for the parent drug, sponsors and/or applicants should contact the appropriate review division to determine whether the parent drug should be measured and analyzed statistically. 

Isotope dilution in combination with the substoichiometric principle is applied in various ways. The most important examples are radioimmunoassay for protein analysis and DNA analysis. In radioimmunoassay, radionuclides are used as tracers and immunochemical reactions for isolation. Radioimmunoassay was first described in 1959 by Yalow and Berson, and since then has found very broad application in clinical medicine, in particular for the measurement of serum proteins, hormones, enzymes, viruses, bacterial antigens, drugs and other substances in blood, other body fluids and tissues. Only one drop of blood is needed, and the analysis can be per-fonned automatically. Today more than 10 immunoassays are made annually in the United States. The most important advantages of the method are the high sensitivity and the high specificity. In favourable cases quantities down to 10 g can... 

It has been increasingly evident that the response of vascular beds to heat in tumors differs considerably firom that in normal tissues. The effective clinical use of hyperthermia depends on a careful application of these biological priiKiples emerging from experimental work. More experimental measurements of temperature response are needed for different tumor types at different ages. It is also important to evaluate the applicability of the dynamic response measrrred in animal to human subjects. Another issue to be addressed is the hyperthermia-itrduced blood flow change in drug delivery, since the reduced tumor blood flow may decrease the drug delivered to the tumors. 

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