Onset of Effect of 5‐HT1B/1D Agonists: A Model With Pharmacokinetic Validation

  title={Onset of Effect of 5‐HT1B/1D Agonists: A Model With Pharmacokinetic Validation},
  author={Anthony W Fox},
  journal={Headache: The Journal of Head and Face Pain},
  • A. Fox
  • Published 1 February 2004
  • Medicine
  • Headache: The Journal of Head and Face Pain
Objective.—To quantitate onset of effect of all formulations of sumatriptan, and to investigate whether this is related to rate, not extent, of drug absorption. 
Resolution of Concentration–Response Differences in Onset of Effect Between Subcutaneous and Oral Sumatriptan
Whether the concentration–response relationships for onset of effect of oral and subcutaneous sumatriptan differ, and if so, then to explore whether a single model for the onset ofeffect can nonetheless be found for multiple dose sizes and both routes of administration.
Rapid Oral Transmucosal Absorption of Sumatriptan, and Pharmacodynamics in Acute Migraine
Whether sumatriptan can be absorbed across the oral mucosa, and, if so, whether there are pharmacodynamic correlates of such pharmacokinetics in patients experiencing migraine attacks, is investigated.
Improved Pharmacokinetics of Sumatriptan With Breath Powered™ Nasal Delivery of Sumatriptan Powder
The purpose of this study was to directly compare the pharmacokinetic (PK) profile of 22‐mg sumatriptan powder delivered intranasally with a novel Breath Powered™ device against a 20‐mg liquid nasal spray, a 100‐mg oral tablet, and a 6‐mg subcutaneous injection.
Theory-based analysis of clinical efficacy of triptans using receptor occupancy
Receptor occupancy can be used as a parameter for a common index to evaluate the therapeutic effect and provide useful information to support the proper use of triptans.
Rapid absorption of sumatriptan powder and effects on glyceryl trinitrate model of headache following intranasal delivery using a novel bi‐directional device
The pharmacokinetics of intranasal sumatriptan (administered using a novel bi‐directional powder delivery device) and its effects on quantitative electroencephalography in patients with migraine were investigated.
Why pharmacokinetic differences among oral triptans have little clinical importance: a comment
If no oral formulations are found that can allow more predictable pharmacokinetics, the same problems will probably also arise with new classes of drugs for the acute treatment of migraine.
Selective reduction in the expression of UGTs and SULTs, a novel mechanism by which piperine enhances the bioavailability of curcumin in rat
It is concluded that piperine pre‐treatment time‐dependently improves the bioavailability of curcumin through the reversible and selective inhibition of UGTs and SULTs.
nhanced oral bioavailability of docetaxel in rats by four consecutive days of retreatment with curcumin
In order to improve the oral bioavailability of docetaxel, a component of turmeric, curcumin, which can down-regulate the intestinal P-glycoprotein and CYP3A protein levels, was used for the pre-treatment of rats before the oral administration of docentaxel.
Interindividual variability of oral sumatriptan pharmacokinetics and of clinical response in migraine patients
The slow rate and low extent of absorption of the drug during the first 2 h after dosing observed in patients of group B could explain their unsatisfactory response to oral sumatriptan.
Prediction of Headache Response in Migraine Treatment
The objective of this investigation was to develop a disease model to predict measures of headache in randomized placebo-controlled clinical trials investigating oral sumatriptan as a paradigm compound and demonstrate the value of combining pharmacokinetic and efficacy information to model disease and characterize time-independent drug properties in a population of migraineurs.


Differentiating the Efficacy of 5‐HT1B/1D Agonists
Examination of clinical trials of serotonin (5‐HT1B/1D) agonists as acute treatments for migraine to examine whether transformation of efficacy data into therapeutic gain or number needed to treat is useful.
Comparison of Therapeutic Gain With Therapeutic Ratio for the Assessment of Selective 5HT1B/1D Agonist Efficacy in Migraine
Comparison of use of therapeutic gain and therapeutic ratio for relative assessments of selective 5HT1B/1D agonist efficacy in the acute treatment of migraine is compared.
Comparative clinical pharmacokinetics of single doses of sumatriptan following subcutaneous, oral, rectal and intranasal administration.
Is There a Preferred Triptan?
The triptan’s high degree of selectivity distinguishes this class of medication from older antimigraine agents such as ergotamine tartrate and dihydroergotamine, which bind to adrenergic, dopaminergic, and other serotonin receptors.
The clinical pharmacology, pharmacokinetics and metabolism of sumatriptan.
Sumatriptan produced a number of minor adverse events, but had no clinically significant effect on routine haematological or biochemical investigations using the intravenous, subcutaneous or oral routes.
A theory of drug action based on the rate of drug-receptor combination
  • W. Paton
  • Biology
    Proceedings of the Royal Society of London. Series B. Biological Sciences
  • 1961
A theory of drug action developed on the assumption that excitation by a stimulant drug is proportional to the rate of drug-receptor combination, rather than to the proportion of receptors occupied by the drug, accounts for the persistence of effect of an antagonist on a tissue.
Migraine Headache Recurrence: Relationship to Clinical, Pharmacological, and Pharmacokinetic Properties of Triptans
Some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class.
Comparison of four basic models of indirect pharmacodynamic responses
Four basic models for characterizing indirect pharmacodynamic responses after drug administration have been developed and compared and it was found that the responses produced showed a slow onset and a slow return to baseline.
Occupancy of alpha 1-adrenergic receptors and contraction of rat vas deferens.
The results suggest that rat vas deferens contains a homogeneous population of alpha 1-adrenergic receptors mediating the contractile response to norepinephrine, that these receptors can be directly labeled with 125IBE, and that there may be a nonlinear relationship between agonist occupancy ofalpha 1- adrenergic receptor-mediated contractile responses and the functional response of this tissue.
Assessing the Onset of Relief of a Treatment for Migraine
  • E. Laska, C. Siegel
  • Medicine, Psychology
    Cephalalgia : an international journal of headache
  • 2000
It is illustrated how the model can be used to help determine how long patients without onset should wait before further intervention, how patients interpret the phrase meaningful relief, and how baseline clinical characteristics affect the onset.