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Drug bioavailability and pharmacokinetic analysis from pharmacological data

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Conclusions

The objective of pharmacotherapy is to control drug effects rather than drug levels. Direct chemical assay data are always of secondary interest and are of value only in that plasma levels often correlate with pharmacological or toxic response.

The use of methodologies of control theory, signal processing, and optimization, borrowed from engineering practice, allow the relations between drug inputs to be directly related to multiple, simultaneously occurring drug responses. These relations also permit time optimal drug inputs to be computed which optimize a multiple drug response behavior and represent a maximum therapeutic utility for the drug (8,9).

In practice, such time optimal drug inputs may be achieved by programmed intravenous or other parenteral administration; such optimal response behavior may less precisely be realized through a predetermined dosage regimen with a drug product possessing the required dynamic drug bioavailability behavior. With the advent of increasingly more sophisticated biomedical recording and signal processing instrumentation and the increasing computerization of hospitals, it is not difficult to envisage that a maximum therapeutic utility of one or several drugs' actions may be automatically and continuously maintained using closed-loop feedback control. The process can be envisaged to involve monitoring of the patient's multiple drug responses and processing of the signals to compute an optimal pharmacotherapeutic control input signal, which in turn actuates servomechanistic drug-adminstering devices which deliver the drug(s) at the rate(s) required to maintain the patient's drug response behavior at optimal levels. In addition to the work now being pursued in the authors' laboratory, progress in approaching such ideals in pharmacotherapy is presently exemplified by the artificial “beta cell” developed by Whitaker Space Sciences which utilizes biofeedback controlled delivery of insulin in response to the patient's blood glucose levels.

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Smolen, V.F., Weigand, W.A. Drug bioavailability and pharmacokinetic analysis from pharmacological data. Journal of Pharmacokinetics and Biopharmaceutics 1, 329–336 (1973). https://doi.org/10.1007/BF01060040

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