Microdose: The New Drug Development Approach

Abstract

The development process of new drugs is very complex, expensive and time consuming process. The development process consists of several steps, including animal studies and human clinical trials. The process relies in general on the understanding of the metabolism pathways and the pharmacokinetics of a drug. During the development process approximately 40% of drug candidates that enters the clinical trials fail to pass through the first human studies (phase 1).Reason for most of the failures is due to inappropriate toxicological and/or PK properties, therefore predetermining the PK value in humans before the drug is tested in the first human clinical trials will lead to a reduced amount of drug failures. Minimizing the amount of failures will also result in a reduction of the drugs developmental cost, from which approximately 75% was based on drug failures in the early stages of the process. Microdosing is a new promising approach that may help reduce both the amount of animal studies needed and the drug development costs. The approach consists of determining pharmacokinetic and pharmacodynamic properties of the candidate drugs in humans in the early phase of the developmental process. In the study a very small dose of the drug defined as less than 100 µg will be administered to human subjects, following the collection of samples in different time intervals and/or the real-time scan of the patients to observe how the compound is distributed in the body. Drug candidates with better PK properties will be selected for further study, whereas the other candidates will be banned. For the practice of microdose study there are ultrasensitive analytical methods needed. The accelerator mass spectrometry (AMS) and the positron emission tomography (PET) are needed to determine the pharmacokinetics and pharmacodynamics of the candidate drugs in humans. Projects such as the CREAM and EUMAPP confirm the predictability of the microdose to determine PK values related to the therapeutic dose. Pediatric drug development process is very complicated, because children are less likely to participate in clinical trials due to ethical issues. Traditionally the dosage of drugs administered to children is obtained from correction of the adult therapeutic dose with bodyweight and body surface area. This indicates that there is the possibility that children could be underdosed or overdosed in relation with the related effect exerted by the drug. A proper dosage of drugs could be obtained by applying the microdose study in children.