Assessment of Pharmacokinetic Drug-Drug Interactions in Humans: In Vivo Probe Substrates for Drug Metabolism and Drug Transport Revisited

Annual Review of Pharmacology and Toxicology
Uwe FuhrFritz Sörgel

Abstract

Pharmacokinetic parameters of selective probe substrates are used to quantify the activity of an individual pharmacokinetic process (PKP) and the effect of perpetrator drugs thereon in clinical drug-drug interaction (DDI) studies. For instance, oral caffeine is used to quantify hepatic CYP1A2 activity, and oral dagibatran etexilate for intestinal P-glycoprotein (P-gp) activity. However, no probe substrate depends exclusively on the PKP it is meant to quantify. Lack of selectivity for a given enzyme/transporter and expression of the respective enzyme/transporter at several sites in the human body are the main challenges. Thus, a detailed understanding of the role of individual PKPs for the pharmacokinetics of any probe substrate is essential to allocate the effect of a perpetrator drug to a specific PKP; this is a prerequisite for reliably informed pharmacokinetic models that will allow for the quantitative prediction of perpetrator effects on therapeutic drugs, also in respective patient populations not included in DDI studies.

References

Sep 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C N PalmerI R Phillips
Jan 1, 1985·European Journal of Clinical Pharmacology·L D BornemannI H Patel
Apr 1, 1988·Clinical Pharmacology and Therapeutics·K Brøsen, L F Gram
May 1, 1988·Clinical Pharmacology and Therapeutics·D A CirauloJ H Jaffe
Mar 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R A Weisiger
Jan 1, 1983·British Journal of Clinical Pharmacology·P HeizmannW H Ziegler
Jan 1, 1984·Annals of the New York Academy of Sciences·E S Vesell
Jan 1, 1982·European Journal of Clinical Pharmacology·K E PedersenK K Pedersen
Aug 1, 1995·Journal of Clinical Psychopharmacology·P D KrobothR B Smith
May 1, 1996·Clinical Pharmacology and Therapeutics·K E ThummelG R Wilkinson
Jul 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S KeidingP Ott
Sep 5, 1998·Clinical Pharmacology and Therapeutics·J C GorskiS D Hall
Apr 23, 1999·Pharmaceutical Research·R B KimG R Wilkinson
Jul 2, 1999·Virchows Archiv : an International Journal of Pathology·T YokoseK Mukai
Jul 20, 1999·The Journal of Clinical Investigation·B GreinerH K Kroemer
Sep 2, 1999·Pharmacogenetics·D LucasF Berthou
Dec 14, 1999·British Journal of Clinical Pharmacology·K E KenworthyJ B Houston
Dec 12, 2001·British Journal of Clinical Pharmacology·J L PalmerS Pleasance
Jan 5, 2002·Naunyn-Schmiedeberg's Archives of Pharmacology·C Pauli-MagnusM F Fromm
Jul 19, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Andrew WilliamsSteven A Wrighton
Aug 28, 2002·The Annals of Pharmacotherapy·Patrick J McDonnell, Michael R Jacobs
Sep 14, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ina KochLeszek Wojnowski
Dec 24, 2002·Clinical Pharmacology and Therapeutics·Jang-Ik LeeReginald F Frye
Jun 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kiran C PatkiDavid J Greenblatt
Jul 23, 2003·The Journal of Surgical Research·Pierce K H ChowSteven T F Chan
Jan 30, 2004·European Journal of Clinical Pharmacology·Alexander JetterUwe Fuhr
Mar 27, 2004·European Journal of Clinical Pharmacology·Alexander JetterFritz Sörgel
Oct 8, 2004·Clinical Pharmacology and Therapeutics·Andrew L MasicaGrant R Wilkinson
Jan 25, 2006·Clinical Pharmacokinetics·Ann K Daly
May 9, 2006·European Journal of Clinical Pharmacology·Robert Z HarrisDesmond Padhi
Feb 3, 2007·European Journal of Clinical Pharmacology·D FrankU Fuhr
Feb 26, 2008·British Journal of Clinical Pharmacology·R Michael BaldwinLeif Bertilsson

❮ Previous
Next ❯

Citations

Mar 28, 2019·Clinical Pharmacology and Therapeutics·Aleksi TornioJanne T Backman
Sep 13, 2020·Pharmaceutics·Dominique A GarrisonSharyn D Baker
Dec 18, 2020·Clinical Pharmacology in Drug Development·Wan SunMaria Rosario
Jul 23, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Oliver Scherf-ClavelFritz Sörgel
Jan 6, 2021·Pharmaceutics·Young Hee Choi, Young-Won Chin
Apr 29, 2021·Scientific Reports·Natália MartoSofia A Pereira
Jun 3, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Dongyi SunXin Wang
Aug 20, 2021·Basic & Clinical Pharmacology & Toxicology·Aleksi TornioJanne T Backman

❮ Previous
Next ❯

Methods Mentioned

BETA
sedation
dissection
genotyping
urine sampling

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.