Zolmitriptan Intranasal: A Review of the Pharmacokinetics and Clinical Efficacy

Abstract

Migraine is a common disabling neurological disorder, associated with headache, nausea, and on occasions vomiting. Zolmitriptan is a widely available serotonin 5HT(1B/1D) receptor agonist with a long track record in clinical studies and in the treatment of acute migraine. A nasal formulation has been developed that has clear evidence for local absorption, resulting in plasma drug concentrations within 2 minutes of dosing, central nervous system penetration 3 minutes later, and a significant efficacy benefit versus placebo 10 to 15 minutes after dosing. Intranasal zolmitriptan offers advantages to migraineurs, particularly those seeking a more rapid onset of effect without wishing to self-inject, or those with gastrointestinal upset. The comparison of pharmacokinetic and clinical data available from different formulations of zolmitriptan contributes both to the understanding of its mode of action and the characteristics required of an acute migraine treatment if it is to meet patient needs.

A Review of the Pharmacokinetics, Pharmacodynamics and Efficacy of Zolmitriptan in the Acute Abortive Treatment of Migraine

“…[32][33][34][35][36] In addition, the appearance of zolmitriptan's active metabolite in plasma following intranasal administration occurs at about 30 minutes after nasal administration. 37 Thus although first-pass metabolism in the liver is avoided with the nasal spray formulation, it is likely that the active metabolite of zolmitriptan contributes to the lasting effi cacy of the intranasal formulation as with the oral formulations.…”

Implementation of experimental design methodology in preparation and characterization of zolmitriptan loaded chitosan nanoparticles

“…Patients with migraine generally suffer from nausea and vomiting; oral dosage forms can therefore be inconvenient or unacceptable (Uemura et al, 2005). An intranasal administration of ZMT offers advantages to patients, particularly those seeking a more rapid onset of effect (Goadsby and Yates, 2006). The rapid clearance of the drug from the nasal cavity and hepatic metabolism could lead to only 40% absolute bioavailability by nasal and oral administration.…”

Micellar Nanocarriers: Potential Nose-to-Brain Delivery of Zolmitriptan as Novel Migraine Therapy

“…Despite the fact that zolmitriptan is a potent molecule, the current oral therapies present drawbacks, such as slow onset of action, low bioavailability (40-45%), nausea and incomplete pain relief with recurrence of headaches (2,5,6). Additionally, oral zolmitriptan exhibits a short half-life of 1-2 h, with the drug undergoing first-pass metabolism and being rapidly cleared by the hepatic and the renal systems (7). Administration of the nasal solution of the drug in the spray form resulted in a quicker onset of action, providing headache relief within 15 min of administration.…”