title: Microdosing: current and the future.
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.
authors.affiliation: Xceleron Inc., 20340 Seneca Meadows Parkway, Germantown, MD 20876, USA. graham.lappin@xceleron.com
authors.forename: Graham
authors.initials: G
authors.lastname: Lappin
mesh_terms: D000818:Animals; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000639:trends*; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations