Interindividual variability of oral sumatriptan pharmacokinetics and of clinical response in migraine patients

• Published in: European journal of clinical pharmacology 2008-05, Vol.64 (5), p.489-495
• Main Authors: Ferrari, Anna, Pinetti, Diego, Bertolini, Alfio, Coccia, Ciro, Sternieri, Emilio
• Format: Article
• Language: English
• Subjects: Administration, Oral; Area Under Curve; Bioavailability; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Chromatography, High Pressure Liquid; Clinical outcomes; Drug therapy; Female; Half-Life; Humans; Injections, Subcutaneous; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Migraine; Migraine without Aura - drug therapy; Neurology; Pharmacokinetics and Disposition; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Serotonin Receptor Agonists - administration & dosage; Serotonin Receptor Agonists - pharmacokinetics; Serotonin Receptor Agonists - therapeutic use; Sumatriptan - administration & dosage; Sumatriptan - pharmacokinetics; Sumatriptan - therapeutic use; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-007-0443-9

Background The marketing of sumatriptan, a selective serotonin (5-HT) 1B/1D agonist, first of the class of triptans, has increased the therapeutic options for the treatment of migraine attacks. However, almost one third of patients in clinical trials fail to have headache relief after oral administration of sumatriptan. Objective To evaluate whether the interindividual differences in the clinical response following oral administration of sumatriptan are due to differences in its pharmacokinetics. Methods We compared the pharmacokinetics of sumatriptan after oral (100 mg) and subcutaneous (6 mg) administration in two age- and gender-matched groups: ten subjects (group A) with satisfactory response and ten (group B) with unsatisfactory response to oral sumatriptan. Patients were studied during headache-free intervals. Blood samples were taken serially from baseline to 360 min after oral administration and from baseline to 180 min after subcutaneous injection. Sumatriptan plasma concentrations were determined by high-performance liquid chromatography (HPLC) with an electrochemical detector. Results Following oral dosing, patients of group A absorbed sumatriptan significantly faster and achieved early plasma levels significantly higher than patients of group B. The systemic exposure to sumatriptan during the first 2 h, which are the most important for rapid onset of action and for antimigraine efficacy, was significantly greater in group A than in group B ( P