Investigation of sarizotan's impact on the pharmacokinetics of probe drugs for major cytochrome P450 isoenzymes: a combined cocktail trial

European Journal of Clinical Pharmacology
S KrösserA Kovar

Abstract

The 5HT(1A) receptor agonist sarizotan is in clinical development for the treatment of dyskinesia, a potentially disabling complication in Parkinson's disease. We investigated the effect of sarizotan on the clinical pharmacokinetics of probe drugs for cytochrome P450 (CYP) to evaluate the risk of CYP-related drug-drug interactions. This was a double-blind, randomised, two-period cross-over interaction study with repeated administration of 5 mg sarizotan HCl or placebo b.i.d. for 8 days in 18 healthy volunteers. On day 4, a single dose of 100 mg metoprolol (CYP2D6 probe) was administered. On day 8, single doses of 100 mg caffeine (CYP1A2 probe), 50 mg diclofenac (CYP2C9 probe), 100 mg mephenytoin (CYP2C19 probe) and 7.5 mg midazolam (CYP3A4 probe) were simultaneously applied. Pharmacokinetic parameters for probe drugs and their metabolites in plasma and urinary recovery were determined. Concentration-time profiles and pharmacokinetic parameters of all probes and their metabolites remained unchanged after co-administration of sarizotan, compared with placebo. Analysis of variance of the area under the plasma concentration-time curve for probe drugs/metabolites, metabolic ratios and urinary excretion resulted in 90% confidence int...Continue Reading

References

Jun 1, 1990·Clinical Pharmacology and Therapeutics·M V NelsonP A LeWitt
Jan 1, 1983·European Journal of Clinical Pharmacology·C G RegårdhP O Lagerström
Jan 1, 1994·European Journal of Clinical Pharmacology·J T BackmanK T Olkkola
Nov 9, 2000·Clinical Pharmacokinetics·C M Kaye, B Nicholls
Nov 30, 2000·Current Treatment Options in Neurology·I H Richard
Jan 4, 2001·Drug Metabolism Reviews·S A WrightonP B Watkins
Jun 22, 2001·European Journal of Clinical Pharmacology·W J TammingaJ H Jonkman
Aug 2, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G T TuckerS M Huang
Nov 24, 2001·Clinical Pharmacology and Therapeutics·B ZhuH H Zhou
Dec 12, 2001·British Journal of Clinical Pharmacology·J L PalmerS Pleasance
Feb 20, 2002·British Journal of Clinical Pharmacology·Leif BertilssonAyman Al-Shurbaji
Jun 5, 2002·Current Neurology and Neuroscience Reports·Oksana Suchowersky
May 20, 2003·Journal of Clinical Pharmacology·Thorir D BjornssonUNKNOWN Pharmaceutical Research and Manufacturers of America Drug Metabolism/Clinical Pharmacology Technical Working Groups
Jan 30, 2004·Journal of Clinical Pharmacology·Honghui ZhouJames F McLeod
Jan 25, 2005·Drug Metabolism and Drug Interactions·A LeucutaM Nanulescu

❮ Previous
Next ❯

Citations

Aug 27, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jiangquan ZhouSamuel M Poloyac
Apr 8, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Satish Kumar BedadaHarish Kaushik Kotakonda
Aug 28, 2016·International Journal of Pharmaceutics·Marine CamblinMaxim Puchkov
Dec 4, 2015·Phytotherapy Research : PTR·Satish Kumar BedadaPrasad Neerati
Apr 2, 2009·Biological & Pharmaceutical Bulletin·Ying LiuJianshi Lou
Apr 14, 2017·CNS Drugs·Peer Tfelt-HansenJacob Tfelt-Hansen

❮ 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 Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Danielle SmithLucinda Cohen
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
H-H Sherry ChowDavid S Alberts
JAMA : the Journal of the American Medical Association
P K HonigL R Cantilena
Journal of the American Chemical Society
Richard LonsdaleJeremy N Harvey
© 2021 Meta ULC. All rights reserved