Anna Ferrari1, Diego Pinetti, Alfio Bertolini, Ciro Coccia, Emilio Sternieri. 1. Division of Toxicology and Clinical Pharmacology, University Centre for Adaptive Disorders and Headache, Section Modena II, University of Modena and Reggio Emilia, Modena, Italy. annaf@unimore.it
Abstract
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 < 0.001, Student's t test for independent data). On the other hand, after subcutaneous injection of sumatriptan, the profile of the curves was similar in all patients, and there were no differences in pharmacokinetics between group A and group B. CONCLUSION: 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.
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 < 0.001, Student's t test for independent data). On the other hand, after subcutaneous injection of sumatriptan, the profile of the curves was similar in all patients, and there were no differences in pharmacokinetics between group A and group B. CONCLUSION: 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.
Authors: R K Cady; F Sheftell; R B Lipton; S O'Quinn; M Jones; D G Putnam; A Crisp; A Metz; S McNeal Journal: Clin Ther Date: 2000-09 Impact factor: 3.393
Authors: Simona Sacco; Christian Lampl; Faisal Mohammad Amin; Mark Braschinsky; Christina Deligianni; Derya Uludüz; Jan Versijpt; Anne Ducros; Raquel Gil-Gouveia; Zaza Katsarava; Paolo Martelletti; Raffaele Ornello; Bianca Raffaelli; Deirdre M Boucherie; Patricia Pozo-Rosich; Margarita Sanchez-Del-Rio; Alexandra Sinclair; Antoinette Maassen van den Brink; Uwe Reuter Journal: J Headache Pain Date: 2022-10-12 Impact factor: 8.588