Predicting drug candidate victims of drug-drug interactions, using microdosing.

Clinical Pharmacokinetics
Marie CroftGraham Lappin

Abstract

The aim of this crossover human male volunteer study was to investigate the utility of microdosing in the investigation of drug-drug interactions. A 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 inhibit P-glycoprotein and metabolism by cytochrome P450 (CYP) 1A2, CYP3A4 and CYP2C9. When administered alone, pharmacokinetics for all four microdosed compounds scaled well with those reported for therapeutic doses and with previously performed microdose studies. The pharmacokinetics of each compound administered as a microdose were significantly altered after the administration of ketoconazole and fluvoxamine, showing statistically significant (p < 0.01) 12.8-, 8.1- and 3.2-fold increases in the area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) for midazolam, caffeine and fexofenadine, respectively. A 1.8-fold increase (not statistically significant) in AUC(∞) was observed for tolbutamide. The changes in pharmacokinetics mediated by ketoconazole and fluvoxamine were quantitatively consistent with previously reported, non-mi...Continue Reading

References

Feb 1, 1994·British Journal of Clinical Pharmacology·Y S KrishnaiahD Visweswaram
Feb 17, 2001·Clinical Pharmacology and Therapeutics·H MadsenK Brøsen
Sep 25, 2001·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G YoungB Adamkiewicz
Oct 21, 2005·British Journal of Clinical Pharmacology·Kerry E Culm-MerdekDavid J Greenblatt
Dec 6, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Suresh K BalaniGerald T Miwa
Jun 10, 2006·The Journal of Pharmacology and Experimental Therapeutics·Aleksandra Galetin, J Brian Houston
Sep 6, 2006·Clinical Pharmacology and Therapeutics·Graham LappinR Colin Garner
Dec 5, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Akihito OgasawaraEmiko Kazama
May 25, 2007·Drugs·Stephanie K A BlickAntona J Wagstaff
Sep 7, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Naoe YamaneYuji Kumagai
Oct 5, 2007·Journal of Pharmaceutical Sciences·Kan HeScott J Grossman
Mar 24, 2010·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Graham LappinColin Garner
Nov 19, 2010·Bioanalysis·Malcolm Rowland
Nov 19, 2010·Bioanalysis·Graham Lappin

❮ Previous
Next ❯

Citations

Oct 3, 2015·Leukemia & Lymphoma·Pernille SvendsenHans E Johnsen
Apr 5, 2013·Expert Opinion on Drug Metabolism & Toxicology·Graham LappinTal Burt
Aug 29, 2012·Journal of Pharmaceutical Sciences·Malcolm Rowland
Jan 16, 2015·British Journal of Clinical Pharmacology·Nicolas HohmannGerd Mikus
Feb 11, 2014·International Journal of Cancer. Journal International Du Cancer·Gregory T Wurz, Michael W Degregorio
Jul 24, 2015·Nucleic Acids Research·Richard NovakRichard A Mathies
May 1, 2015·Clinical Pharmacokinetics·Nicolas HohmannGerd Mikus
Jun 18, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yukari UmeyamaTeruaki Okuda
Feb 27, 2016·Clinical and Translational Science·T BurtM Rowland
Jun 22, 2019·British Journal of Clinical Pharmacology·Nicolas HohmannWalter E Haefeli
Nov 6, 2012·Expert Review of Clinical Pharmacology·Janne Hukkanen
Sep 10, 2020·Nature Reviews. Drug Discovery·Tal BurtYuichi Sugiyama
Mar 21, 2013·Clinical Pharmacology and Therapeutics·B HalamaW E Haefeli
Apr 29, 2019·Clinical Pharmacokinetics·Merel van NulandJos H Beijnen
Sep 1, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Tal BurtRobert J Noveck
Jul 15, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jennifer LangAleksandra Galetin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

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.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

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.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Derrek A HeuvelingGuus A M S van Dongen
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Astrid A M van der VeldtAdriaan A Lammertsma
International Journal of Clinical Pharmacology and Therapeutics
Ichiro IeiriYuichi Sugiyama
© 2022 Meta ULC. All rights reserved