Predictive Value of Microdose Pharmacokinetics

Clinical Pharmacokinetics
M Van NulandJ H Beijnen


Phase 0 microdose trials are exploratory studies to early assess human pharmacokinetics of new chemical entities, while limiting drug exposure and risks for participants. The microdose concept is based on the assumption that microdose pharmacokinetics can be extrapolated to pharmacokinetics of a therapeutic dose. However, it is unknown whether microdose pharmacokinetics are actually indicative of the pharmacokinetics at therapeutic dose. The aim of this review is to investigate the predictive value of microdose pharmacokinetics and to identify drug characteristics that may influence the scalability of these parameters. The predictive value of microdose pharmacokinetics was determined for 46 compounds and showed adequate predictability for 28 of 41 orally administered drugs (68%) and 15 of 16 intravenously administered drugs (94%). Microdose pharmacokinetics were considered predictive if the mean observed values of the microdose and the therapeutic dose were within twofold. Nonlinearity may be caused by saturation of enzyme and transporter systems, such as intestinal and hepatic efflux and uptake transporters. The high degree of success regarding linear pharmacokinetics shows that phase 0 microdose trials can be used as an early...Continue Reading


May 1, 1978·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P R ReevesM J Winrow
May 1, 1979·Journal of Clinical Pharmacology·C T ViswanathanP G Welling
Sep 1, 1979·European Journal of Clinical Pharmacology·P J PentikäinenA Penttilä
Apr 20, 1977·European Journal of Clinical Pharmacology·M D RawlinsA R Hijab
Aug 1, 1992·Clinical Pharmacology and Therapeutics·H FriedmanS F Francom
Jan 1, 1992·Critical Reviews in Toxicology·S A Wrighton, J C Stevens
Jun 1, 1991·Journal of Medicinal Chemistry·F P GuengerichP Berntsson
Apr 1, 1990·Biopharmaceutics & Drug Disposition·J M ScavoneDavid J Greenblatt
Jul 1, 1990·Journal of Clinical Pharmacology·K J SimonsF E Simons
Jan 1, 1989·The Journal of Infection·P A Cload
May 1, 1974·Journal of Clinical Pharmacology·K S AlbertJ G Wagner
Apr 1, 1984·Clinical Pharmacology and Therapeutics·C G MeredithS Schenker
Aug 1, 1980·Clinical Pharmacology and Therapeutics·R SpectorM M Ghoneim
Jun 1, 1994·British Journal of Clinical Pharmacology·E ChanMalcolm Rowland
Sep 1, 1993·Naunyn-Schmiedeberg's Archives of Pharmacology·H K KroemerM Eichelbaum
Jul 15, 1998·British Journal of Clinical Pharmacology·J O Miners, D J Birkett
Dec 26, 2001·Clinical Pharmacology and Therapeutics·K SugimotoA Fujimura
Jun 18, 2003·Clinical Pharmacology and Therapeutics·Yohei NishizatoYuichi Sugiyama
Oct 11, 2003·Journal of Clinical Pharmacology·Katsutoshi OgawaKatsuji Oguchi
Mar 18, 2004·British Journal of Clinical Pharmacology·Ichiro FukazawaHajime Yasuhara
Mar 27, 2004·European Journal of Clinical Pharmacology·Alexander JetterFritz Sörgel
Aug 3, 2004·Nature Reviews. Drug Discovery·I Kola, John Landis
May 18, 2005·Journal of Clinical Pharmacy and Therapeutics·K ChenS-Q Wang
Jul 15, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Maki ShimizuYuichi Sugiyama
Jul 19, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Takehito YamamotoTatsuji Iga
Jul 21, 2005·Clinical Pharmacokinetics·Domenic A SicaSiddhartha Ghosh
Oct 21, 2005·British Journal of Clinical Pharmacology·Kerry E Culm-MerdekDavid J Greenblatt
Nov 8, 2005·Drug Metabolism and Pharmacokinetics·Naoko KimuraKen-Ichi Inui
Apr 14, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Naoki IshiguroYuichi Sugiyama
Apr 22, 2006·The Journal of Pharmacology and Experimental Therapeutics·Lichuan LiuK Sandy Pang
May 12, 2006·Molecular Pharmaceutics·Lei ZhangShiew-Mei Huang
Sep 6, 2006·Clinical Pharmacology and Therapeutics·Graham LappinR C Garner
Oct 6, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tomoko AkutsuKan Chiba
Dec 29, 2006·Clinical Pharmacology and Therapeutics·Y Y LauLeslie Z Benet
Jan 5, 2007·Biological & Pharmaceutical Bulletin·Shigeo ShinodaYoko Ohe
Aug 24, 2007·Clinical Pharmacology and Therapeutics·M IwamotoJ A Wagner
Dec 22, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H S LeeI J Jang
Jan 19, 2008·Clinical Pharmacology and Therapeutics·I Kola
Dec 2, 2008·Expert Opinion on Drug Metabolism & Toxicology·Graham Lappin, R C Garner
Jun 16, 2009·British Journal of Clinical Pharmacology·Ajay MadanHaig P Bozigian
Sep 30, 2009·British Journal of Pharmacology·A Kalliokoski, M Niemi
Mar 24, 2010·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Graham LappinColin Garner
May 12, 2010·Journal of Clinical Pharmacy and Therapeutics·A YamazakiM Maeda
May 28, 2010·Pharmacogenomics·Ekaitz Errasti-Murugarren, Marçal Pastor-Anglada
Sep 8, 2010·Clinical Pharmacokinetics·Nathanael L Dirks, Bernd Meibohm
Sep 23, 2010·Handbook of Experimental Pharmacology·Maurice J Arnaud
Dec 24, 2010·British Journal of Clinical Pharmacology·Landry K KamdemZeruesenay Desta
Jan 19, 2011·Clinical Pharmacokinetics·Garry G GrahamKenneth M Williams
May 4, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Francesco TrottaGiovanni Tafuri
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
Jul 1, 2011·Clinical Pharmacology and Therapeutics·Kazuya MaedaYuichi Sugiyama
Aug 6, 2011·The AAPS Journal·Leslie Z BenetTudor I Oprea
Aug 11, 2011·The Journal of Pharmacy and Pharmacology·Vidya PereraAndrew J McLachlan
Oct 14, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Anthony HarrisonPaul Turnpenny
Feb 18, 2012·Clinical Pharmacokinetics·Marie CroftGraham Lappin
Nov 29, 2012·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Jianmeng ChenEdward J Fuchs
Mar 21, 2013·Clinical Pharmacology and Therapeutics·B HalamaWalter E Haefeli
Apr 5, 2013·Expert Opinion on Drug Metabolism & Toxicology·Graham LappinTal Burt
Apr 9, 2013·Journal of the American College of Cardiology·Jeffrey D WesslerRobert P Giugliano
Jun 4, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Toshihiko IkedaYuichi Sugiyama
Aug 29, 2013·Biochemical and Biophysical Research Communications·Yumi HashiguchiHideyuki Saito
Aug 31, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Nachum KaplanBarry Hafkin
Mar 13, 2014·British Journal of Clinical Pharmacology·T PrueksaritanontS A Stoch
Jan 16, 2015·British Journal of Clinical Pharmacology·Nicolas HohmannGerd Mikus
Apr 9, 2015·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Priska KaufmannHideya Mukai
Apr 15, 2015·Clinical Pharmacology and Therapeutics·Maria L H VlamingWouter H J Vaes
Jun 8, 2015·Pharmacogenetics and Genomics·Liudmila L MazaleuskayaTeri E Klein
Aug 25, 2015·Cancer Chemotherapy and Pharmacology·Ken-Ichi FujitaYasutsuna Sasaki
Oct 11, 2015·Clinical Pharmacology and Therapeutics·Malcolm Rowland
Dec 13, 2016·Clinical Pharmacology and Therapeutics·T PrueksaritanontS A Stoch
Apr 15, 2017·Drug Design, Development and Therapy·Gab-Jin ParkDong-Seok Yim
Apr 18, 2017·Journal of Pharmaceutical Sciences·Jingjing YuIsabelle Ragueneau-Majlessi
May 13, 2017·Journal of Pharmaceutical Sciences·Xiaomin Liang, Kathleen M Giacomini
Jan 13, 2018·The Journal of Pharmacology and Experimental Therapeutics·Yi-An BiManthena V S Varma
Mar 9, 2018·Journal of Advanced Nursing·Beatriz Martín-Del-RíoGemma Benavides-Gil
Jun 22, 2018·Drug Discovery Today·Dennis A SmithMalcolm Rowland


Jan 24, 2020·Clinical Pharmacology in Drug Development·M Van NulandJ H Beijnen
Sep 10, 2020·Nature Reviews. Drug Discovery·Tal BurtYuichi Sugiyama
Apr 28, 2020·Expert Opinion on Drug Metabolism & Toxicology·Kathrin I Foerster, Jürgen Burhenne

Related Concepts

Clinical Trials
Drug Kinetics
Liver Function
Membrane Transport Proteins
Determination Aspects
Pharmacologic Substance

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Systemic Juvenile Idiopathic Arthritis

Systemic juvenile idiopathic arthritis is a rare rheumatic disease that affects children. Symptoms include joint pain, as well as fevers and skin rashes. Here is the latest research on this disease.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Cell Atlas Along the Gut-Brain Axis

Profiling cells along the gut-brain axis at the single cell level will provide unique information for each cell type, a three-dimensional map of how cell types work together to form tissues, and insights into how changes in the map underlie health and disease of the GI system and its crosstalk with the brain. Disocver the latest research on single cell analysis of the gut-brain axis here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Pontocerebellar Hypoplasia

Pontocerebellar hypoplasias are a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. Here is the latest research on pontocerebellar hypoplasia.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.


Trichotillomania is an impulse control disorder characterized by the recurrent pulling of one's hair resulting in noticeable hair loss. Here are the latest discoveries in this field.

DDX3X Syndrome

DDX3X syndrome is caused by a spontaneous mutation at conception that primarily affects females due to its location on the X-chromosome. DDX3X syndrome has been linked to intellectual disabilities, seizures, autism, low muscle tone, brain abnormalities, and slower physical developments. Here is the latest research.