Design of drug delivery strategies based on well-stirred experiments

Abstract

Drugs are generally administered to the human body via injections (IV) or through other paths such as the buccal, nasal routes. The main consideration when designing a medication schedule is to maintain a therapeutic level of the drug in the body during the course of treatment. To achieve this goal, when IV drug therapy is selected, particular importance has to given to the dose to be injected and how to maintain the concentration of the pharmaceutical active ingredient (API) in the body between a Minimum Toxic Concentration (MTC) and a Minimum Effective Concentration (MEC). This therapeutic range varies with the drug and is designed so that the patient takes full benefit of the treatment while keeping potential risks or side effects to a minimum. The aim of this thesis is to design drug administration protocols based on well- stirred vessel experiments that mimic one- and two-compartment pharmacokinetic models. A one-compartment model assumes that drug is evenly distributed in the body, which is represented by a beaker with an inlet and an outlet stream. In a two- compartment model, drug is distributed between the central and peripheral vessels. Only bolus and constant-rate infusion are considered in this study. Mathematical models are used to estimate the pharmacokinetic parameters and to derive administration strategies to be tested experimentally. Results show that the well-stirred vessel captures the behavior of one- and two-compartment models very well. The time-concentration profiles of a tracer in the compartments are functions of the kinetic parameters

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