The combination of indomethacin, prochlorperazine and caffeine (IPC) is often overused by migraine patients who develop medication-overuse headache (MOH), a secondary chronic headache that resolves after withdrawal of the overused medication. In a previous study (1) we showed that indomethacin clearance was lower in chronic migraine patients overusing IPC combination than in migraine patients only occasionally taking this combination. Objective: To verify if the reduced clearance of indomethacin reverts to normal after withdrawal of the overused IPC. Methods: We repeated the study of indomethacin pharmacokinetics in 9 female headache patients after 6 months from inpatient withdrawal of the IPC combination. In each patients indomethacin pharmacokinetics had been already studied before withdrawal treatment. The IPC combination (indomethacin 50 mg, prochlorperazine 8 mg, caffeine150 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. Pharmacokinetic parameters were calculated by means of the P K Solutions 2.0 program. Results: The pharmacokinetic parameters of indomethacin in 4 patients (group A) who relapsed in IPC overuse were similar to those observed before withdrawal treatment; instead (Table 1) in 5 patients (group B) who steadily discontinued IPC combination, indomethacin disposition was significantly different from that observed before withdrawal treatment. Table 1. Pharmacokinetic parameters of indomethacin in group B. Parameter Before withdrawal After withdrawalHalf life (h) 2.74+0.98 1.45+0.34 *AUC0-t (mg/h/ml) 13.02+6.62 5.36+2.36 *Cl (ml/h/Kg) 64.05+30.16 123.98+39.91 * *P <0.05 (paired Student’ t-test)Conclusions: In headache patients who discontinued IPC overuse, indomethacin clearance increased and reverted to values previously obtained in occasional IPC users (1).1. Ferrari A., Savino G., Gallesi D., Pinetti D., Bertolini A., Sances G., et al. (2006) Pharmacol Res. 542: 142-149.
Pharmacokinetics of indomethacin in chronic migraine patients after withdrawal of the overused combination of indomethacin, prochlorperazine, and caffeine / Ferrari, Anna; Gallesi, D; Sances, G; Pinetti, D; Bertolini, A; Sternieri, E.. - ELETTRONICO. - (2007), pp. 1-1.
Pharmacokinetics of indomethacin in chronic migraine patients after withdrawal of the overused combination of indomethacin, prochlorperazine, and caffeine
FERRARI, Anna;
2007
Abstract
The combination of indomethacin, prochlorperazine and caffeine (IPC) is often overused by migraine patients who develop medication-overuse headache (MOH), a secondary chronic headache that resolves after withdrawal of the overused medication. In a previous study (1) we showed that indomethacin clearance was lower in chronic migraine patients overusing IPC combination than in migraine patients only occasionally taking this combination. Objective: To verify if the reduced clearance of indomethacin reverts to normal after withdrawal of the overused IPC. Methods: We repeated the study of indomethacin pharmacokinetics in 9 female headache patients after 6 months from inpatient withdrawal of the IPC combination. In each patients indomethacin pharmacokinetics had been already studied before withdrawal treatment. The IPC combination (indomethacin 50 mg, prochlorperazine 8 mg, caffeine150 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. Pharmacokinetic parameters were calculated by means of the P K Solutions 2.0 program. Results: The pharmacokinetic parameters of indomethacin in 4 patients (group A) who relapsed in IPC overuse were similar to those observed before withdrawal treatment; instead (Table 1) in 5 patients (group B) who steadily discontinued IPC combination, indomethacin disposition was significantly different from that observed before withdrawal treatment. Table 1. Pharmacokinetic parameters of indomethacin in group B. Parameter Before withdrawal After withdrawalHalf life (h) 2.74+0.98 1.45+0.34 *AUC0-t (mg/h/ml) 13.02+6.62 5.36+2.36 *Cl (ml/h/Kg) 64.05+30.16 123.98+39.91 * *P <0.05 (paired Student’ t-test)Conclusions: In headache patients who discontinued IPC overuse, indomethacin clearance increased and reverted to values previously obtained in occasional IPC users (1).1. Ferrari A., Savino G., Gallesi D., Pinetti D., Bertolini A., Sances G., et al. (2006) Pharmacol Res. 542: 142-149.
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