Introduction

Pharmacokinetics (PK) is a fairly recent domain of science that has emerged in the fifties of the twentieth century. At that time, PK was construed as being a concern within the domain of pharmacology. From an historic perspective, the first papers addressing pure kinetic matters appeared as late as 1937 by Toresten Teorell. Also, the first textbook concerned with drug kinetics, entitled Der Blutspiegel (Blood Mirror), was published by Dost in Germany in 1953. After two decades, PK was acknowledged as an independent scientific discipline in Bethesda - Maryland in 1972. It is during this period that the entirety of the mathematical foundations of this new science has been accomplished. To this effect, many notable scholars have their prolific and pioneering contributions. These included Krüger - Theimer, J. Wagner, M. Gibaldi and E. Welson.

It is worthwhile mentioning that despite the continued advances in many aspects of the kinetic theory, PK remained mainly focused in the prediction of drugs levels in the body. This characteristic of PK made it a fundamental tool within the context of dosage regimen individualization in clinical practice.

It could be also argued that many of the existing of PK models has not been fully employed in the arena of clinical practice. This assumption is based on the realization that the utilization of these models in such practice remained mainly confined to single point estimation of drugs in the systemic circulation. Despite is relevance, profiling of drugs levels in the human body remained lacking in almost all clinical PK textbooks. This has precluded the chance of gaining a detailed view of the time course of drugs levels in the body. Notwithstanding, interest in modelling of multiple dosing is gaining increasing interest and is consequently provided in some off-the-shelf computer applications in a simplistic manner.

Although many single- and multiple-compartment PK models have been developed over the past decades, it could be demonstrated that the PK of the vast majority of drugs may be adequately described by a single-compartment linear models. This is based on the realization that the multiple compartment features become insignificant in cases where drugs are administered by intravenous infusion or via oral routes. Also, such features become less prominent upon multiple-dosing regimens where steady state condition has been attained. For these reasons, single-compartment models representing different routes of administration where used for the construction of PK-Works. Higher PK linear models would be contemplated in the future editions of the system if such addition is deemed necessary from user’s perspective.

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