Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Graham LappinColin Garner

Abstract

A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (su...Continue Reading

References

May 1, 1979·Journal of Clinical Pharmacology·C T ViswanathanP G Welling
Feb 1, 1978·Journal of Clinical Pharmacology·C T ViswanathanP G Welling
Feb 1, 1979·British Journal of Clinical Pharmacology·E Perucca, A Richens
Apr 20, 1977·European Journal of Clinical Pharmacology·M D RawlinsA R Hijab
May 1, 1992·Antimicrobial Agents and Chemotherapy·S Y ChuJ C Cavanaugh
Nov 1, 1992·Journal of Clinical Pharmacology·S Y ChuC Craft
Nov 1, 1992·Antimicrobial Agents and Chemotherapy·S Y ChuR C Sonders
Jan 1, 1992·Journal of Clinical Pharmacology·S Y ChuJ C Cavanaugh
Jan 1, 1991·European Neurology·P A FowlerN S Baber
Sep 1, 1991·The Journal of Hospital Infection·P G Davey
Jul 1, 1991·Clinical Pharmacokinetics·J T HiiE D Burgess
Jan 1, 1990·European Journal of Clinical Pharmacology·S VozehF Follath
Feb 1, 1989·Journal of Clinical Pharmacology·E BurgessP Wilkes
Jan 1, 1988·European Journal of Clinical Pharmacology·P GianiR Latini
May 1, 1974·Journal of Clinical Pharmacology·K S AlbertJ G Wagner
Aug 1, 1984·Journal of Pharmaceutical Sciences·M E Morris, G Levy
Nov 14, 1984·The American Journal of Cardiology·L A SiddowayR L Woosley
Oct 1, 1980·British Journal of Clinical Pharmacology·L F Prescott
Mar 1, 1982·Clinical Pharmacokinetics·J A ForrestL F Prescott
Feb 1, 1982·Journal of Clinical Pharmacology·E NelsonD Perrier
Apr 1, 1982·Journal of the American Geriatrics Society·M DivollD J Greenblatt
Jan 1, 1982·European Journal of Clinical Pharmacology·A J WilenskyS P Kaluzny
Jul 15, 1981·Biochemical Pharmacology·K Sandy Pang, J A Terrell
Jan 1, 1995·European Journal of Clinical Pharmacology·L F LaceyP A Fowler
Nov 1, 1994·Clinical Pharmacokinetics·A K Scott
Sep 1, 1993·Clinical Pharmacokinetics·F FraschiniG Demartini
May 29, 2002·Fundamental & Clinical Pharmacology·Gerd BodeICH Expert Working Group
Mar 4, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hiroshi Komura, Masahiro Iwaki
Jun 30, 2005·Journal of Pharmaceutical Sciences·Manthena V S Varma, Ramesh Panchagnula
Feb 10, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mary F PaineDarryl C Zeldin
Feb 14, 2006·Biochemical Pharmacology·Donald E Mager
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Graham LappinR C Garner
Mar 29, 2007·Journal of Clinical Pharmacology·Joseph S BertinoAmerican College of Clinical Pharmacology
Sep 7, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Naoe YamaneY Kumagai
Jan 9, 2008·European Journal of Clinical Pharmacology·Anna FerrariEmilio Sternieri
Dec 2, 2008·Expert Opinion on Drug Metabolism & Toxicology·Graham Lappin, R C Garner
Jun 16, 2009·British Journal of Clinical Pharmacology·Lionel D Lewis
Mar 24, 2010·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Graham LappinColin Garner
Nov 19, 2010·Bioanalysis·G Lappin
Dec 15, 2010·Journal of Pharmacokinetics and Pharmacodynamics·K Sandy Pang, Matthew R Durk
Feb 10, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Helen E CubittAleksandra Galetin

Citations

Dec 6, 2011·Archives of Pharmacal Research·Soo Kyung Bae, Ji-Hong Shon
Jun 4, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Toshihiko IkedaYuichi Sugiyama
Sep 14, 2012·Drug Metabolism and Pharmacokinetics·Naoe YamaneY Sugiyama
Dec 4, 2014·European Journal of Drug Metabolism and Pharmacokinetics·Natacha LenuzzaHenri Bénech
Oct 3, 2015·Leukemia & Lymphoma·Pernille SvendsenHans E Johnsen
Apr 5, 2013·Expert Opinion on Drug Metabolism & Toxicology·Graham LappinTal Burt
Jun 13, 2012·Expert Opinion on Drug Metabolism & Toxicology·Miriam G MooijSaskia N de Wildt
Aug 29, 2012·Journal of Pharmaceutical Sciences·Malcolm Rowland
May 4, 2016·Clinical Pharmacology in Drug Development·G Lappin
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
Oct 14, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Anthony HarrisonPaul Turnpenny
Feb 27, 2016·Clinical and Translational Science·Tal BurtMalcolm Rowland
Oct 12, 2014·Drug Discovery Today·Philipp UhlWalter Mier
Oct 12, 2016·Chemical Research in Toxicology·Heather A EnrightKenneth W Turteltaub
Jul 11, 2017·Expert Opinion on Drug Metabolism & Toxicology·Mike UferJasper Dingemanse
Sep 10, 2020·Nature Reviews. Drug Discovery·Tal BurtYuichi Sugiyama
Nov 24, 2017·British Journal of Clinical Pharmacology·Malek OkourJohn Haselden
Jul 28, 2020·Journal of Veterinary Pharmacology and Therapeutics·Irene SartiniMario Giorgi
Jun 21, 2016·The Journal of Veterinary Medical Science·Akiyo SawaguchiMinoru Shimoda
Dec 30, 2016·Future Science OA·Le Thuy VuongStephen R Dueker
Feb 6, 2017·Clinical Pharmacokinetics·Miriam G MooijSaskia N de Wildt
Apr 29, 2019·Clinical Pharmacokinetics·Merel van NulandJos H Beijnen

Related Concepts

Acamol
Carbon Radioisotopes
High Pressure Liquid Chromatography Procedure
Dose-Response Relationship, Drug
Intravenous Injections
Luminal
Propamerck
Mass Spectrometry
Biaxin
Imigran

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.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

The Tendon Seed Network

Tendons are rich in the extracellular matrix and are abundant throughout the body providing essential roles including structure and mobility. The transcriptome of tendons is being compiled to understand the micro-anatomical functioning of tendons. Discover the latest research pertaining to the Tendon Seed Network 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.

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.

Incretins

Incretins are metabolic hormones that stimulate a decrease in glucose levels in the blood and they have been implicated in glycemic regulation in the remission phase of type 1 diabetes. Here is the latest research.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Long COVID-19

“Long Covid-19” describes illness in patients who are reporting long-lasting effects of the SARS-CoV-19 infection, often long after they have recovered from acute Covid-19. Ongoing health issues often reported include low exercise tolerance and breathing difficulties, chronic tiredness, and mental health problems such as post-traumatic stress disorder and depression. This feed follows the latest research into Long Covid.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.