Relevance of absorption rate and lag time to the onset of action in migraine

Clinical Pharmacokinetics
Hugo J MaasOscar E Della Pasqua

Abstract

The objective of this analysis was to simulate the performance of oral triptan formulations with varying absorption characteristics and their impact on the onset and magnitude of the antimigraine effect using a Markov model for migraine attacks. Sumatriptan pharmacokinetic data were obtained from clinical pharmacology studies in which marketed solid formulations were administered. Based on a population pharmacokinetic model, mean concentration-time profiles were generated by varying the absorption rate constant and lag time. Subsequently, the simulated profiles were evaluated in a disease model of migraine to predict the onset and duration of the effect (the pain-free, pain-relief response). Based on a therapeutic dose of 50 mg of sumatriptan, a maximum gain in the pain-free response of 12% was achieved with an increased absorption rate. This gain in the response was reached approximately 0.5 hours after administration. A decrease only in the lag time with respect to the currently available formulations (i.e. 0.24 hours) resulted in a maximum gain of 5% in the pain-free response, which in contrast may not be interpreted as clinically relevant. Model-based predictions suggest that increases in the absorption rate of the currentl...Continue Reading

References

Jul 1, 1978·Clinical Pharmacokinetics·G N Volans
Oct 31, 1998·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·C DuquesnoyE Fuseau
Jul 14, 1999·Cephalalgia : an International Journal of Headache·S P AhrensW H Visser
Nov 15, 2000·Cephalalgia : an International Journal of Headache·G M DaviesR Lipton
Feb 13, 2001·Cephalalgia : an International Journal of Headache·P Tfelt-HansenUNKNOWN International Headache Society Clinical Trials Subcommittee
May 15, 2002·Headache·X Henry HuUNKNOWN United States Migraine Study Protocol (USMAP) Group
Jan 6, 2004·Annals of Neurology·Rami BursteinMoshe Jakubowski
Jun 18, 2004·Current Medical Research and Opinion·Christine WallsJagdev Sidhu
Jul 24, 2004·CNS Drugs·Alan M RapoportFred D Sheftell
Jul 28, 2004·Neurology·Elizabeth Loder
Mar 25, 2006·Cephalalgia : an International Journal of Headache·H J MaasO E Della Pasqua
Mar 27, 2007·Statistics in Medicine·Vladimir V AnisimovOscar Della Pasqua

❮ Previous
Next ❯

Citations

Jan 1, 1974·European Journal of Clinical Pharmacology·P BättigD Walz
May 7, 2011·Drug Development and Industrial Pharmacy·Yukako ItoKanji Takada
Sep 30, 2010·The Journal of Headache and Pain·Anna FerrariEmilio Sternieri
Mar 23, 2012·Headache·Florian Oberhardt, Anthony W Fox
Jun 10, 2017·Journal of Clinical Pharmacology·Arindam PalSagar Munjal

❮ 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.