Frontiers in Pharmacology
July 25, 2024
Yasunori Aoki, Malcom Rowland, Yuichi Sugiyama
Intra-Target Microdosing (ITM), integral to Phase 0 clinical studies, offers a novel approach in drug development, effectively bridging the gap between preclinical and clinical phases. This methodology is especially relevant in streamlining early drug development stages. Our research utilized a Physiologically Based Pharmacokinetic (PBPK) model and Monte Carlo simulations to examine factors...
Frontiers in Pharmacology
July 16, 2024
H. Markus Weiss, Yuichi Sugiyama, Esther van Duijn
Editorial on the Research Topic Incorporating Phase 0 microdosing as a powerful tool into a new vision of drug developmentPhase 0 microdosing, the testing of compounds at subtherapeutic doses in human to enable early decisions in drug discovery and development has been utilized for some years.The uptake was slow even though the concept is attractive and the pre-clinical safety package enabling...
Nature Reviews Drug Discovery
September 8, 2020
Tal Burt, Graeme Young, Wooin Lee et al.
101 citations
Phase 0 approaches - which include microdosing - evaluate subtherapeutic exposures of new drugs in first-in-human studies known as exploratory clinical trials. Recent progress extends phase 0 benefits beyond assessment of pharmacokinetics to include understanding of mechanism of action and pharmacodynamics. Phase 0 approaches have the potential to improve preclinical candidate selection and...
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 & Therapeutics
August 10, 2011
Kazuya Maeda, Yasumasa Ikeda, Tomoe Fujita et al.
207 citations
Clearance of atorvastatin occurs through hepatic uptake by organic anion transporting polypeptides (OATPs) and subsequent metabolism by cytochrome P450 (CYP) 3A4. To demonstrate the relative importance of OATPs and CYP3A4 in the hepatic elimination of atorvastatin in vivo, a clinical cassette microdose study was performed. A cocktail consisting of a microdose of atorvastatin along with probe...
Clinical Pharmacology & Therapeutics
June 29, 2011
Kazuya Maeda, Junichi Takano, Yasumasa Ikeda et al.
50 citations
Microdosing studies are effective in enabling the early identification of the pharmacokinetic properties of compounds administered to humans. However, the nonlinearity of the pharmacokinetics between microdose and therapeutic dose, attributable to the saturation of metabolic enzymes and transporters, is a major concern. Verapamil and quinidine are good substrates of both the multidrug...
The Journal of Clinical Pharmacology
May 19, 2011
Ichiro Ieiri, Yohei Doi, Kazuya Maeda et al.
106 citations
The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally...
Advanced Drug Delivery Reviews
October 14, 2010
Yuichi Sugiyama, Shinji Yamashita
60 citations
The microdose (MD) clinical study enables to select a "better" compound for new drug candidate that shows desirable PK profiles in human. This new methodology is highly expected to streamline the drug development and to increase the success probability in the clinical trial. Since only a small amount of the test compound (less than 100 μg) is administered, the risk of harmful events to a human...