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
Pharmacokinetics and pharmacodynamics of oral diazepam: effect of dose, plasma concentration, and time
Pharmacokinetics of diphenhydramine and a demethylated metabolite following intravenous and oral administration
Disposition of warfarin enantiomers and metabolites in patients during multiple dosing with rac-warfarin
Biomedical applications of accelerator mass spectrometry-isotope measurements at the level of the atom
Macromolecular adduct formation and metabolism of heterocyclic amines in humans and rodents at low doses
Accelerator mass spectrometry in pharmaceutical research and development--a new ultrasensitive analytical method for isotope measurement
Comparative pharmacokinetics of coumarin anticoagulants L: Physiologic modeling of S-warfarin in rats and pharmacologic target-mediated warfarin disposition in man
Evaluation of microdosing strategies for studies in preclinical drug development: demonstration of linear pharmacokinetics in dogs of a nucleoside analog over a 50-fold dose range
The application of accelerator mass spectrometry to absolute bioavailability studies in humans: simultaneous administration of an intravenous microdose of 14C-nelfinavir mesylate solution and oral nelfinavir to healthy volunteers
Evaluation of microdosing to assess pharmacokinetic linearity in rats using liquid chromatography-tandem mass spectrometry
A global examination of allometric scaling for predicting human drug clearance and the prediction of large vertical allometry
Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers
Nontraditional approaches to first-in-human studies to increase efficiency of drug development: will microdose studies make a significant impact?
American College of Clinical Pharmacology position statement on the use of microdosing in the drug development process
2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug
Pharmacokinetic investigation of imatinib using accelerator mass spectrometry in patients with chronic myeloid leukemia
Use of accelerator mass spectrometry to measure the pharmacokinetics and peripheral blood mononuclear cell concentrations of zidovudine
Microdosing assessment to evaluate pharmacokinetics and drug metabolism in rats using liquid chromatography-tandem mass spectrometry
The development of phase I cancer trial methodologies: the use of pharmacokinetic and pharmacodynamic end points sets the scene for phase 0 cancer clinical trials
Single-dose escalation and multiple-dose safety, tolerability, and pharmacokinetics of IDX899, a candidate human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor, in healthy subjects
Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies
Effective use of microdosing and Positron Emission Tomography (PET) studies on new drug discovery and development
A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects
Microdose clinical trial: quantitative determination of nicardipine and prediction of metabolites in human plasma
Microdose pharmacokinetics of IDX899 and IDX989, candidate HIV-1 non-nucleoside reverse transcriptase inhibitors, following oral and intravenous administration in healthy male subjects
Biotransformation profiling of [(14)C]ixabepilone in human plasma, urine and feces samples using accelerator mass spectrometry (AMS)
Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS
The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part III: the three microdose candidates
Accelerator mass spectrometry measurement of intracellular concentrations of active drug metabolites in human target cells in vivo
Microdosing: a valuable tool for accelerating drug development and the role of bioanalytical methods in meeting the challenge
Trends in microdosing and other exploratory human pharmacokinetic studies for early drug development
A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil
PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 2: comparative assessment of prediction methods of human volume of distribution
Clinical relevance of liquid chromatography tandem mass spectrometry as an analytical method in microdose clinical studies
PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 4: prediction of plasma concentration-time profiles in human from in vivo preclinical data by using the Wajima approach
PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 1: goals, properties of the PhRMA dataset, and comparison with literature datasets
Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers
PHRMA CPCDC initiative on predictive models of human pharmacokinetics, part 5: prediction of plasma concentration-time profiles in human by using the physiologically-based pharmacokinetic modeling approach
PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 3: comparative assessement of prediction methods of human clearance
Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects.
Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose
Nonlinear pharmacokinetics of oral quinidine and verapamil in healthy subjects: a clinical microdosing study
Identification of the rate-determining process in the hepatic clearance of atorvastatin in a clinical cassette microdosing study
Prediction of nonlinear intestinal absorption of CYP3A4 and P-glycoprotein substrates from their in vitro Km values
Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms
Microdosing studies using accelerated mass spectrometry as exploratory investigational new drug trials
Calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry assays and its application in supporting microdose absolute bioavailability studies
Best practice in the use of physiologically based pharmacokinetic modeling and simulation to address clinical pharmacology regulatory questions
Pharmacogenomic/pharmacokinetic assessment of a four-probe cocktail for CYPs and OATPs following oral microdosing
Ultrasensitive liquid chromatography-tandem mass spectrometric methodologies for quantification of five HIV-1 integrase inhibitors in plasma for a microdose clinical trial
Biphasic elimination of tenofovir diphosphate and nonlinear pharmacokinetics of zidovudine triphosphate in a microdosing study
A microdose study of ¹⁴C-AR-709 in healthy men: pharmacokinetics, absolute bioavailability and concentrations in key compartments of the lung
An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development
To Apply Microdosing or Not? Recommendations to Single Out Compounds with Non-Linear Pharmacokinetics
Observational infant exploratory [(14)C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis
Human absorption, distribution, metabolism and excretion properties of drug molecules: a plethora of approaches
Intra-Target Microdosing - A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans
Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation
Pharmacokinetics, Excretion, and Mass Balance of [14 C]-Batefenterol Following a Single Microtracer Intravenous Dose (Concomitant to an Inhaled Dose) or Oral Dose of Batefenterol in Healthy Men
Preclinical Characterization and Human Microdose Pharmacokinetics of ITMN-8187, a Nonmacrocyclic Inhibitor of the Hepatitis C Virus NS3 Protease
Determination of [11C]rifampin pharmacokinetics within Mycobacterium tuberculosis-infected mice by using dynamic positron emission tomography bioimaging
Sex-specific neurobiological actions of prophylactic (R,S)-ketamine, (2R,6R)-hydroxynorketamine, and (2S,6S)-hydroxynorketamine.
Stable Isotopically Labeled Intravenous Microdose Pharmacokinetic Trials as a Tool to Assess Absolute Bioavailability: Feasibility and Paradigm to Apply for Protein Kinase Inhibitors in Oncology
Successful Use of [14 C]Paracetamol Microdosing to Elucidate Developmental Changes in Drug Metabolism
Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease
Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14 C-microtracer and therapeutic dose in cancer patients
Combining Isotopic Tracer Techniques to Increase Efficiency of Clinical Pharmacokinetic Trials in Oncology
Intra-Target Microdosing (ITM): A Novel Drug Development Approach Aimed at Enabling Safer and Earlier Translation of Biological Insights Into Human Testing
Phase 0, including microdosing approaches: Applying the Three Rs and increasing the efficiency of human drug development
Relevance of In Vitro Metabolism Models to PET Radiotracer Development: Prediction of In Vivo Clearance in Rats from Microsomal Stability Data
Dynamic imaging in patients with tuberculosis reveals heterogeneous drug exposures in pulmonary lesions.
Human microdosing and mice xenograft data of AGM-130 applied to estimate efficacious doses in patients
Innovative Approaches for Pharmacology Studies in Pregnant and Lactating Women: A Viewpoint and Lessons from HIV.
Phase-0/microdosing studies using PET, AMS, and LC-MS/MS: a range of study methodologies and conduct considerations. Accelerating development of novel pharmaceuticals through safe testing in humans - a practical guide
A Phase 1, Open-Label Study in Healthy Subjects to Evaluate the Absolute Bioavailability of AG-221 by a Microtracer Approach
A Multipurpose First-in-Human Study With the Novel CXCR7 Antagonist ACT-1004-1239 Using CXCL12 Plasma Concentrations as Target Engagement Biomarker.
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