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Pharmacol. Migraine is a neurological disease that affects all age categories. However, the fea- tures of the headache attacks which are associated with migraine vary with age. As a consequence, the effectiveness of medication aborting these attacks also depends on a patient’s age. Quantitative knowledge of the relationship between drug effects and age can guide the establishment of the most effective treatment regimens for the different age categories. The current analysis aims to quantify such relationship for the oral formulation of the anti-migraine drug sumatriptan. A time-inhomogeneous Markov model has been developed to describe the progres- sion of a migraine attack over three clinically defined stages (“no relief”, “relief” and “pain free”). The transition rates determining the progression along these stages are nonlinear functions of both the drug concentration in plasma and the age of the patient. Model parameters were estimated using data from clinical trials of oral sumatriptan in adolescents and adults (range 12 – 65 years). The rates at which the pain relief and pain free states are attained are inversely related to age. The midpoints of these relationships are located at 23 (20 – 27) and 22 (17 – 27) years, respectively (mean and 95% confidence interval). In the absence of drug, the mean transit time from “no relief” to “relief” is ∼3 h for adolescent patients and ∼6 h for patients aged 28 and over. Oral sumatriptan therapy reduces these transit times to 2 h, irrespective of age. In conclusion, the Markov model captures the characteristics of the relationship be- tween age and the effectiveness of oral sumatriptan therapy. This approach can be applied to predict the age-dependent response to other forms of anti-migraine.
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