Effect of overuse of the antimigraine combination of indomethacin, prochlorperazine and caffeine (IPC) on the disposition of its components in chronic headache patients

Anna Ferrari, Gustavo Savino, Daniela Gallesi, Diego Pinetti, Alfio Bertolini, Grazia Sances, Ciro Pio Rosario Coccia, Gabriella Pasciullo, Sheila Leone, Marianna Loi, Emilio Sternieri

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The combination of indomethacin, prochlorperazine and caffeine (IPC) is one of the most utilized formulations for the treatment of migraine attacks in Italy. Several patients suffering from chronic headache overuse this symptomatic medication in the attempt to control their headache. Objective: To verify whether overuse of IPC combination by chronic headache patients is associated with modified disposition of its components. Methods: We studied indomethacin, prochlorperazine, and caffeine disposition in 34 female subjects suffering from primary headaches, subdivided into four groups: eight migraine patients occasionally using IPC combination suppositories-group 1; nine patients with chronic headache and probable medication-overuse headache, daily taking one or more suppositories of the IPC combination-group 2; 11 migraine patients occasionally using "mild" suppositories of the IPC combination-group 3; six migraine patients occasionally taking tablets of the IPC combination-group 4. The IPC combination habitually used was administered to each patient. Blood samples were taken at baseline and at fixed intervals up to 6 h after administration. Plasma levels of indomethacin and prochlorperazine were assayed by high-pressure liquid chromatographic (HPLC) method; caffeine levels were assayed by enzyme multiplied immunoassay test (EMIT). Pharmacokinetic parameters were calculated by means of a computer software (P K Solutions 2.0. Summit Research Services, Montrose, CO, USA). Results: Half-life of indomethacin was longer, and clearance lower, in group 2 than in the other groups; AUC of indomethacin in group 2 was twice that in group 1 (P <0.05, Newman-Keuls' test). Peak concentrations and AUC0→∞ of caffeine were significantly higher in group 2 than in the other groups (P <0.05, Newman-Keuls' test). We could not define prochlorperazine disposition because it was not detectable in the majority of blood samples. Conclusion: Overuse of IPC combination in chronic headache patients is associated with increased plasma levels of indomethacin and caffeine, and with delayed elimination of indomethacin; the high and sustained concentrations of these drugs may cause rebound headache, organ damages, and perpetuate medication-overuse headache.

Original languageEnglish
Pages (from-to)142-149
Number of pages8
JournalPharmacological Research
Volume54
Issue number2
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Caffeine
  • Indomethacin
  • Medication-overuse headache
  • Pharmacokinetics
  • Prochlorperazine

ASJC Scopus subject areas

  • Pharmacology

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