Kinetics of indomethacin in headache patients who abitually take an association of indomethacin, caffeine and prochlorperazine

Indomethacin, in combination with prochlorperazine and caffeine (IPC), is often overused by migraine patients who develop medication-overuse headache. Indomethacin clearance is lower in chronic migraine patients overusing IPC combination than in migraine patients only occasionally taking it. Objective: to verify if indomethacin reduced clearance reverts to normal after withdrawal of the overused IPC combination. Methods: We repeated the study of indomethacin pharmacokinetics in 9 female chronic migraine patients after 3 months from inpatient withdrawal treatment from IPC combination overuse. The IPC combination (indomethacin 50 mg, prochlorperazine 8 mg, caffeine 150 mg) habitually taken was administered by rectal route to each patient. Blood samples were drawn before dosing and at the following post-dose times: 0.5, 1, 2, 3, 4, and 6 h. Indomethacin concentrations were measured by HPLC method. Results: Pharmacokinetic parameters of indomethacin in 4 patients who relapsed into IPC overuse were similar to those observed before withdrawal treatment; on the other hand, indomethacin clearance reverted to values consistent with published data in 5 patients who discontinued IPC combination overuse. Conclusions: Indomethacin normal clearance was related to a reduced frequency of migraine; conversely, indomethacin delayed clearance sustained medication-overuse headache.