Prediction of headache response in migraine treatment.
Triptans are efficacious for the acute treatment of migraine attacks. Yet, defining a concentration-effect relation for these compounds is difficult as the dynamics of the migraine attack are not thoroughly understood. 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. A hidden Markov model based on the states of response (no relief, relief, and pain free) and headache scores (observed variable) was used in conjunction with population pharmacokinetics. Model parameters were capable of predicting the course of headache relief, pain-free status and headache recurrence. It was shown that sumatriptan shortens mean transit times between states by up to 5 h. The potency of sumatriptan (EC(50)) was 9 ng/ml. These findings demonstrate the value of combining pharmacokinetic and efficacy information to model disease and characterize time-independent drug properties in a population of migraineurs.
Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, the Netherlands.
H J
HJ
Maas
M
M
Danhof
O E
OE
Della Pasqua
D015897:Comorbidity; D003198:Computer Simulation; D020000:Decision Support Systems, Clinical; D004305:Dose-Response Relationship, Drug; D006261:Headache / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D008390:Markov Chains; D008881:Migraine Disorders / Q000188:drug therapy* / Q000453:epidemiology*; D008954:Models, Biological; D015233:Models, Statistical; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011379:Prognosis; D012189:Retrospective Studies; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D018170:Sumatriptan / Q000008:administration & dosage*; D013813:Therapy, Computer-Assisted / Q000379:methods*; D016896:Treatment Outcome
D017366:Serotonin Receptor Agonists; D018170:Sumatriptan