Clinical and Translational Science
February 26, 2016
Tal Burt, K Yoshida, Graham Lappin et al.
91 citations
Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities favor limited exposure clinical trials such as microdosing and other phase 0 trials. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure. An increasing number...
Clinical Pharmacology in Drug Development
November 1, 2015
Graham Lappin
AbstractThe concept of microdosing has been around for more than a decade. It consists of the subpharmacologic administration of an investigational drug (1% of the pharmacologic dose or 100 µg, whichever is lower) to human subjects to attain pre–phase 1 pharmacokinetics (PK) in humans. The major concern with microdosing has been the potential for nonlinear PK between doses, but methods are...
Expert Opinion on Drug Metabolism & Toxicology
April 4, 2013
Graham Lappin, Robert J. Noveck, Tal Burt
97 citations
INTRODUCTION: Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. AREAS COVERED: The authors...
Clinical Pharmacokinetics
February 16, 2012
Marie Croft, Brendan J. Keely, Ian D. Morris et al.
42 citations
ObjectiveThe aim of this crossover human male volunteer study was to investigate the utility of microdosing in the investigation of drug-drug interactions.MethodsA mixture of midazolam, tolbutamide, caffeine and fexofenadine were administered as a microdose (25 μg each) before and after administration of a combined pharmacological dose of ketoconazole (400 mg) and fluvoxamine (100 mg) to...
Bioanalysis
March 1, 2010
Graham Lappin
36 citations
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...
Expert Opinion on Drug Metabolism & Toxicology
November 28, 2008
Graham Lappin, R Colin Garner
89 citations
BACKGROUND: Microdosing studies (human Phase 0) are used to select drug candidates for Phase I clinical trials on the basis of their pharmacokinetic properties, using subpharmacologic doses (maximum 100 microg). There are questions as to whether pharmacokinetic data obtained at these low doses will predict those at the clinically relevant dose. OBJECTIVE: To review the current literature on...
Clinical Pharmacology & Therapeutics
September 1, 2006
Graham Lappin, W. Kuhnz, R. Jochemsen et al.
242 citations
OBJECTIVES: A volunteer trial was performed to compare the pharmacokinetics of 5 drugs--warfarin, ZK253 (Schering), diazepam, midazolam, and erythromycin--when administered at a microdose or pharmacologic dose. Each compound was chosen to represent a situation in which prediction of pharmacokinetics from either animal or in vitro studies (or both) was or is likely to be problematic. METHODS: In...
Nature Reviews Drug Discovery
February 28, 2003
Graham Lappin, R. Colin Garner
257 citations
The process of early clinical drug development has changed little over the past 20 years despite an up to 40% failure rate associated with inappropriate drug metabolism and pharmacokinetics of candidate molecules. A new method of obtaining human metabolism data known as microdosing has been developed which will permit smarter candidate selection by taking investigational drugs into humans...