Titre du document / Document title

The novel anti-migraine compound zolmitriptan (Zomig 311C90) has no clinically significant interactions with paracetamol or metoclopramide

Auteur(s) / Author(s)

SEABER E. J. ⁽¹⁾ ; RIDOUT G. ⁽¹⁾ ; LAYTON G. ⁽¹⁾ ; POSNER J. ⁽¹⁾ ; PECK R. W. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Glaxo Wellcome Research and Development, Greenford Road, Greenford, Middlesex UB6 OHE, ROYAUME-UNI

Résumé / Abstract

Objective: This study investigated potential pharmacokinetic or pharmacodynamic interactions between the novel anti-migraine compound zolmitriptan (Zomig, formerly 311C90) and paracetamol and/or metoclopramide. Methods: In an open-label, randomised, crossover study, 15 healthy volunteers received single oral doses of 10 mg zolmitriptan alone, 1 g paracetamol alone, 10 mg zolmitriptan + 1 g paracetamol, 10 mg zolmitriptan + 10 mg metoclopramide or 10 mg zolmitriptan + 1 g paracetamol + 10 mg metoclopramide on five separate occasions. Results: Metoclopramide had no significant effects on the pharmacokinetics of zolmitriptan or the active zolmitriptan metabolite 183C91, nor did it affect interactions between zolmitriptan and paracetamol. Paracetamol marginally increased the maximum plasma concentration (C_max) (11%) and the area under the curve (AUC) (111%) and reduced the renal clearance of zolmitriptan (9%); similar small effects were seen on 183C91. The AUC, C_max and half-life of paracetamol were reduced by concomitant zolmitriptan (by 11%, 31% and 8%, respectively), whilst the mean residence time showed a small increase (+0.7 h). There was a trend towards a transient increase in blood pressure following all regimens containing zolmitriptan; this effect was small, was consistent between all zolmitriptan regimens as well as with previous studies, and was considered to be clinically insignificant. Zolmitriptan was well tolerated after all treatment regimens. Conclusion: Concomitant administration of zolmitriptan and paracetamol resulted in a slight increase in bioavailability of zolmitriptan and a reduced rate and extent of paracetamol absorption. These findings are considered to be of no clinical significance and there is no reason to avoid concomitant administration of paracetamol and/or metoclopramide with zolmitriptan.

Revue / Journal Title

European journal of clinical pharmacology   ISSN 0031-6970 

Source / Source

1997, vol. 53, n^o3-4, pp. 229-234 (25 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, Berlin, ALLEMAGNE  (1970) (Revue)

Mots-clés anglais / English Keywords

Zolmitriptan ; Antimigrainous agent ; Paracetamol ; Analgesic ; Metoclopramide ; Antiemetic ; D2 Dopamine receptor ; Drug combination ; Drug interaction ; Human ; Metabolism ; Pharmacokinetics ; Randomization ; Crossover study ; Single dose ; Oral administration ; Benzamide derivatives ; Dosage adjustment ;

Mots-clés français / French Keywords

Zolmitriptan ; Antimigraineux ; Paracétamol ; Analgésique ; Métoclopramide ; Antiémétique ; Récepteur dopaminergique D2 ; Association médicamenteuse ; Interaction médicamenteuse ; Homme ; Métabolisme ; Pharmacocinétique ; Randomisation ; Essai croisé ; Dose unique ; Voie orale ; Benzamide dérivé ; Ajustement posologie ;

Mots-clés espagnols / Spanish Keywords

Zolmitriptán ; Agente antimigrañoso ; Paracetamol ; Analgésico ; Metoclopramida ; Antiemético ; Receptor dopaminérgico D2 ; Asociación medicamentosa ; Interacción medicamentosa ; Hombre ; Metabolismo ; Farmacocinética ; Aleatorización ; Ensayo cruzado ; Dosis única ; Vía oral ; Benzamida derivado ;

Localisation / Location

INIST-CNRS, Cote INIST : 13739, 35400007989032.0110