Microdosing: Current and The Future

Microdosing, a technique used for about ten years, allows researchers to compare the pharmacokinetics of a very low drug dose with those at a therapeutic dose. About 80% of available microdose pharmacokinetic data scale within a twofold difference of therapeutic doses. The method is expanding beyond pharmacokinetic prediction into areas like studying drug-drug interactions, where volunteers receive a microdose before and after an enzyme-inhibiting or -inducing drug. It also helps obtain early metabolic profiles by administering a 14C-labeled drug and comparing total and unchanged compound concentrations. Microdosing is now being applied to assess drug concentrations in key cell or tissue types, broadening its use in drug development.

Study at a glance

Abstract

The concept of microdosing has been around for approximately 10 years. In this time there have been an increasing number of drugs reported in the literature where the pharmacokinetics at a microdose have been compared with those observed at a therapeutic dose. Currently, approximately 80% of the microdose pharmacokinetics available in the public domain have been shown to scale to those observed at a therapeutic dose, within a twofold difference. Microdosing is now being extended into areas of drug development other than purely pharmacokinetic prediction. Microdosing has been applied to the study of drug-drug interactions by giving human volunteers a microdose of the candidate drug before and after the administration of a drug known to inhibit or induce certain enzymes, such as the cytochrome P450s. Early data on the metabolism of a drug candidate can be obtained by administering a (14)C-drug to human volunteers and comparing the plasma concentration-time curves for total (14)C and unchanged parent compound. Full metabolic profiles can be generated as an early indication of the drug's metabolism in humans, prior to Phase 1 clinical studies. Microdosing is also being applied to situations where the concentration of a drug in cell or tissue types is key to its efficacy. The application of microdosing as a tool in drug development is therefore widening into new and previously unforeseen fields.