Microdosing and drug development: past, present and future

Expert Opinion on Drug Metabolism & Toxicology
Graham LappinTal Burt

Abstract

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. The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directi...Continue Reading

References

May 1, 1979·Journal of Clinical Pharmacology·C T ViswanathanP G Welling
Nov 11, 1975·Clinical Pharmacology and Therapeutics·J M StrongA J Atkinson
Aug 1, 1992·Clinical Pharmacology and Therapeutics·H FriedmanS F Francom
Jan 1, 1991·European Neurology·P A FowlerN S Baber
Sep 1, 1991·The Journal of Hospital Infection·P G Davey
Feb 1, 1992·British Journal of Cancer·E S NewlandsM H Brampton
Jun 1, 1989·Clinical Pharmacokinetics·P D Garzone, P D Kroboth
May 1, 1974·Journal of Clinical Pharmacology·K S AlbertJ G Wagner
Jun 1, 1994·British Journal of Clinical Pharmacology·E ChanMalcolm Rowland
May 12, 1997·Mutation Research·Kenneth W TurteltaubN Shen
Mar 31, 1999·Rapid Communications in Mass Spectrometry : RCM·J Barker, R Colin Garner
Mar 4, 2003·Nature Reviews. Drug Discovery·Graham Lappin, R Colin Garner
Apr 6, 2005·Drug Discovery Today·R Colin Garner
Dec 6, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Suresh K BalaniGerald T Miwa
Dec 22, 2005·Frontiers in Bioscience : a Journal and Virtual Library·Ciro ParlatoAldo Moraci
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Graham LappinR Colin Garner
Sep 6, 2006·Clinical Pharmacology and Therapeutics·Graham LappinR Colin Garner
Mar 29, 2007·Journal of Clinical Pharmacology·Joseph S BertinoAmerican College of Clinical Pharmacology
Jul 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alex Sparreboom
Jul 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alan V BoddyStephen G O'Brien
Apr 22, 2008·Analytical Chemistry·Mehran SalehpourHelge Bryhni
Jun 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·A Hilary Calvert, Ruth Plummer
Dec 2, 2008·Expert Opinion on Drug Metabolism & Toxicology·Graham Lappin, R Colin Garner
Apr 15, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shivaani KummarJames H Doroshow
Jun 16, 2009·British Journal of Clinical Pharmacology·Ajay MadanHaig P Bozigian
May 12, 2010·Journal of Clinical Pharmacy and Therapeutics·A YamazakiM Maeda
Aug 24, 2010·Bioorganic & Medicinal Chemistry Letters·Jane L WangJeffery Carter
Nov 19, 2010·Bioanalysis·Malcolm Rowland
Nov 19, 2010·Bioanalysis·Graham Lappin
May 5, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Graham LappinColin Garner
Jun 2, 2011·Journal of Pharmaceutical Sciences·Malcolm Rowland, Leslie Z Benet
Jun 22, 2011·Pharmacogenetics and Genomics·Ichiro IeiriYuichi Sugiyama
Aug 6, 2011·The AAPS Journal·Leslie Z BenetTudor I Oprea
Oct 14, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Anthony HarrisonPaul Turnpenny
Dec 6, 2011·Archives of Pharmacal Research·Soo Kyung Bae, Ji-Hong Shon
Feb 18, 2012·Clinical Pharmacokinetics·Marie CroftGraham Lappin
Apr 14, 2012·British Journal of Clinical Pharmacology·Thor OstenfeldPhillip Jeffrey
Aug 3, 2012·International Journal of Clinical Pharmacology and Therapeutics·Ichiro IeiriY Sugiyama
Aug 29, 2012·Journal of Pharmaceutical Sciences·Malcolm Rowland
Sep 5, 2012·Bioanalysis·L T VuongB Goldstein
Nov 29, 2012·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Jianmeng ChenEdward J Fuchs

Citations

Oct 3, 2015·Leukemia & Lymphoma·Pernille SvendsenHans E Johnsen
Oct 11, 2015·Clinical Pharmacology and Therapeutics·Malcolm Rowland
May 4, 2016·Clinical Pharmacology in Drug Development·Graham Lappin
Jul 24, 2015·Nucleic Acids Research·Richard NovakRichard A Mathies
Jul 22, 2014·British Journal of Clinical Pharmacology·Claire BeaumontMalcolm A Young
Jun 23, 2015·Clinical Pharmacology and Therapeutics·M A TurnerSaskia N de Wildt
Feb 27, 2016·Clinical and Translational Science·Tal BurtMalcolm Rowland
Feb 13, 2014·Clinical Pharmacology and Therapeutics·C Oo, K L Duchin
Dec 22, 2016·Journal of Labelled Compounds & Radiopharmaceuticals·A F RoffelE-J van Hoogdalem
Jan 25, 2018·Behavioral Sciences·Lázara Martínez Muñoz
Aug 18, 2017·Angewandte Chemie·Jens AtzrodtMarc Reid
Aug 15, 2017·Pharmacology Research & Perspectives·Rajkumar CheluvappaRajaraman Eri
May 18, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Briana K ChenChristine A Denny
Sep 10, 2020·Nature Reviews. Drug Discovery·Tal BurtYuichi Sugiyama
Feb 6, 2017·Clinical Pharmacokinetics·Miriam G MooijSaskia N de Wildt
Apr 29, 2019·Clinical Pharmacokinetics·Merel van NulandJos H Beijnen
Jun 20, 2020·Drug Metabolism Reviews·Lianne J StevensEvita van de Steeg
Nov 24, 2017·British Journal of Clinical Pharmacology·Malek OkourJohn Haselden
Apr 28, 2020·Expert Opinion on Drug Metabolism & Toxicology·Kathrin I Foerster, Jürgen Burhenne
Jun 30, 2017·Cancer Chemotherapy and Pharmacology·Wan-Su ParkDong-Seok Yim

Related Concepts

Dose-Response Relationship, Drug
Drug Interactions
Pharmaceutical Preparations
Toxicokinetics
Microdosing Trials, Human
Positron-Emission Tomography
Intravenous Administration
Drug Kinetics
Positron-Emission Tomography
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