The effects of moclobemide on the pharmacokinetics of the 5-HT1B/1D agonist rizatriptan in healthy volunteers.

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Van Haarst AD, Van Gerven JM, Cohen AF, De Smet M, Sterrett A, Birk KL, Fisher AL, De Puy ME, Goldberg MR, Musson DG

The effects of moclobemide on the pharmacokinetics of the 5-HT1B/1D agonist rizatriptan in healthy volunteers.

Br J Clin Pharmacol. 1999 Aug;48(2):190-6.

PubMed ID

10417495 [ View in PubMed

]

Abstract

AIMS: The new 5-HT1B/1D agonist rizatriptan (MK-0462) has recently been registered for the treatment of migraine. Its primary route of metabolism is via monoamine oxidase-A (MAO-A). Antidepressants such as the MAO-A inhibitor moclobemide may be used in patients with chronic headache syndromes. Hence, this study aimed to investigate the interactions between rizatriptan and moclobemide. METHODS: In a double-blind, randomized, placebo-controlled, two-period cross-over study 12 healthy, young volunteers (six males, six females) were treated with moclobemide (150 mg twice daily) or placebo for 4 days. On the fourth day, a single dose of rizatriptan (10 mg) was administered, and subsequently blood and urine samples were collected for assay of rizatripan and N-monodesmethyl rizatriptan. Plasma concentrates of 3,4-dihydroxyphenylglycol (DHPG), a marker of MAO-A inhibition, were also assessed. Supine and standing blood pressure were measured regularly. RESULTS: Both treatments were well tolerated. During moclobemide, the increase in supine diastolic blood pressure following rizatriptan administration was augmented. Inhibition of MAO by moclobemide was inferred from a persistent decrease in DHPG level (43% on average). When rizatriptan was coadministered with moclobemide, the area under the plasma drug concentration-time profiles for rizatriptan and its N-monodesmethyl metabolite increased 2.2-fold (90% CI, 1.93-2.47) and 5.3-fold (90% CI, 4.81-5.91), respectively, when compared with placebo. Peak plasma drug concentrations for rizatriptan and its n-monodesmethyl metabolite increased 1.4-fold (90% CI, 1.11-1.80) and 2.6-fold (90% CI, 2.23-3.14), respectively, and half-lives of both were prolonged. CONCLUSIONS: Moclobemide inhibited the metabolism of rizatriptan and its active N-monodesmethyl metabolite through inhibition of MAO-A. Thus, moclobemide may considerably potentiate rizatriptan action. Concurrent administration of moclobemide and rizatriptan is not recommended.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Rizatriptan	Amine oxidase [flavin-containing] A	Protein	Humans	Unknown	Substrate	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Almotriptan Furazolidone	The metabolism of Almotriptan can be decreased when combined with Furazolidone.
Almotriptan Procaine	The metabolism of Almotriptan can be decreased when combined with Procaine.
Almotriptan Tranylcypromine	The metabolism of Almotriptan can be decreased when combined with Tranylcypromine.
Almotriptan Phenelzine	The metabolism of Almotriptan can be decreased when combined with Phenelzine.
Almotriptan Minaprine	The metabolism of Almotriptan can be decreased when combined with Minaprine.