Evaluation of Non-Invasive Techniques to Assess Vasoconstriction in Healthy Volunteers Using Methoxamine as a Probe Drug

Dixon, R S; Meire, HB; Leigh, C.; Posner, John; Rolan, P.

doi:10.1046/j.1468-2982.1996.1607507.x

Cited by 2 publications

(1 citation statement)

References 23 publications

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“…These are important because this study involved the most careful assessment of the peripheral hemodynamics of zolmitriptan in the These techniques were selected because they had previously been shown by the same investigators to be sensitive to the effects of the vasoconstrictor, methoxamine (9). As considerable beat-to-beat variability was noted in the Doppler parameters in the methoxamine study (9), the signal was averaged over 2min in the zolmitriptan study to improve sensitivity in detecting drug-induced changes. The study was conducted in a temperature-controlled environment (25°C) to vasodilate subjects in order that any vasoconstriction could be detected.…”

Section: Ersofanzine/dilz~droer~otaniinementioning

confidence: 99%

Potential drug interactions with the novel antimigraine compound zolmitriptan (Zomig™, 311C90)

Rolan

1997

Cephalalgia

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Seven randomized studies in healthy volunteers have investigated interactions between zolmitriptan (Zomig, formerly 311C90), a 5HT1B/1D agonist for acute migraine therapy, and selected drugs with which there was a possibility of interaction or a likelihood of concurrent use. Co-administration of oral dihydroergotamine, ergotamine, pizotifen, fluoxetine, paracetamol (acetaminophen)/metoclopramide or selegiline had no clinically significant effects on the pharmacokinetics of zolmitriptan or its metabolites, although small changes were observed in some cases. Co-administration of propranolol resulted in a 56% increase in the area under the plasma concentration-time curve (AUC) of zolmitriptan and a 11% decrease in the AUC of the active metabolite 183C91. However, these pharmacokinetic changes are unlikely to be relevant at lower clinical doses. Moclobemide, a monoamine oxidase A (MAO-A) inhibitor, decreased the clearance of zolmitriptan and, in particular, 183C91. This suggests that MAO-A is involved in the metabolism of 183C91 and it may be prudent to limit the daily zolmitriptan dose in migraine patients maintained on a MAO-A inhibitor. The clinically insignificant blood pressure increases produced by zolmitriptan, and the tolerability profile of this agent, were unaffected by any of the concomitant medications. Clinically significant interactions between zolmitriptan and commonly co-prescribed antimigraine therapies are unlikely.

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Section: Ersofanzine/dilz~droer~otaniinementioning

confidence: 99%

Potential drug interactions with the novel antimigraine compound zolmitriptan (Zomig™, 311C90)

Rolan

1997

Cephalalgia

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Peripheral Vascular Effects and Pharmacokinetics of the Antimigraine Compound, Zolmitriptan, in Combination with Oral Ergotamine in Healthy Volunteers

et al. 1997

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Members of the new class of antimigraine compounds, 5HT1B/1D agonists, as well as ergotamine, may cause vasoconstriction through stimulation of 5HT receptors on peripheral vessels. The cardiovascular effects of 20 mg oral zolmitriptan (Zomig, formerly 311C90), 2 mg oral ergotamine and the combination were assessed in a randomized double-blind, placebo-controlled crossover study in 12 healthy subjects. Pharmacodynamic measures included oscillometric blood pressure, systolic blood pressure at the toe and arm using a strain gauge technique, stroke volume and cardiac output using bioimpedance cardiography, high-resolution ultrasound to measure brachial arterial diameter and a novel Doppler method to measure blood flow velocity. Both drugs produced small degrees of peripheral vasoconstriction, including increases in diastolic blood pressure and blood flow velocity and decreases in arterial diameter and toe-arm systolic pressure gradient. These effects were generally additive with the combination but of no clinical importance. There were no significant changes in cardiac output, stroke volume heart rate or ECG. Zolmitriptan, at eight times the likely therapeutic dose, was generally well tolerated both alone and in combination with ergotamine. Ergotamine had no clinically important effects on zolmitriptan pharmacokinetics.

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Evaluation of Non-Invasive Techniques to Assess Vasoconstriction in Healthy Volunteers Using Methoxamine as a Probe Drug

Cited by 2 publications

References 23 publications

Potential drug interactions with the novel antimigraine compound zolmitriptan (Zomig™, 311C90)

Potential drug interactions with the novel antimigraine compound zolmitriptan (Zomig™, 311C90)

Peripheral Vascular Effects and Pharmacokinetics of the Antimigraine Compound, Zolmitriptan, in Combination with Oral Ergotamine in Healthy Volunteers

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