Pharmacokinetics of rizatriptan tablets during and between migraine attacks.

Gastric stasis during migraine attacks results in delayed absorption of several orally administered antimigraine agents. This study, as part of a larger trial, was conducted to examine the pharmacokinetics of rizatriptan tablets during and between migraine attacks. Participating patients met IHS criteria for migraine with or without aura, and suffered between one and eight migraines per month for the previous 6 months. In part 1 of the study, 21 patients were randomized to receive a single 5-mg tablet of rizatriptan or placebo in the migraine-free state. In part 2, the same patients were treated during migraine with rizatriptan 5-mg tablets (n=18) or placebo (n=3). Blood samples were obtained before dosing and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing. The plasma concentration profile (ie, AUC((0-infinity)), C(max), T(max)) of rizatriptan 5-mg tablets administered during and between migraine attacks were comparable. The median T(max) for rizatriptan between and during attacks was 1 hour, indicating rapid absorption even during a migraine attack. Rizatriptan 5 mg was well tolerated and 67% of the patients experienced headache relief 2 hours postdose.

A placebo-controlled crossover study of rizatriptan in the treatment of multiple migraine attacks. Rizatriptan Multiple Attack Study Group.

OBJECTIVE: To examine the safety and efficacy of rizatriptan 10 mg PO in the treatment of multiple migraine attacks. BACKGROUND: Rizatriptan is a potent and rapidly absorbed 5-HT1B/1D receptor agonist. Efficacy and general safety have been examined in controlled trials treating single migraine attacks. In the current placebo-controlled study, we report constancy of safety and efficacy of rizatriptan for patients treating four discrete migraine attacks. METHODS: Patients with moderate or severe migraine (n = 473) were randomized to one of five sequence groups, in which each patient was to treat four migraine attacks. Patients in four groups received rizatriptan 10 mg for three of four attacks and placebo for the remaining attack. Patients in the fifth group received rizatriptan 10 mg for four attacks. Headache severity, functional disability, and migraine symptoms were measured immediately before dosing and at 0.5, 1, 1.5, 2, 3, and 4 hours postdose. RESULTS: After the first attack, response rates were 77% for rizatriptan and 37% for placebo (p < 0.001). Similar efficacy of rizatriptan, ranging from a 75 to 80% response, was observed in each of the subsequent attacks with no evidence of tolerance to therapeutic effects. Most patients (93%) responded to rizatriptan 10 mg during the first or second attack. Adverse experiences were generally mild and transient, the most common being dizziness and somnolence. Incidence of adverse experiences per attack decreased after the first attack. CONCLUSIONS: Rizatriptan 10 mg PO is efficacious and generally well tolerated in acute migraine. Its efficacy is maintained throughout the treatment of multiple, discrete migraine attacks.

Double-blind, placebo-controlled, dose-finding study of rizatriptan (MK-462) in the acute treatment of migraine.

Rizatriptan (MK-462) is a potent 5HTID receptor agonist. This multicenter, double-blind, placebo-controlled, outpatient study investigated the clinical efficacy, safety, and tolerability of rizatriptan (2.5, 5, and 10 mg) as a function of dose for acute migraine. Patients with moderate or severe migraine (n = 417) were treated with placebo (n = 67), rizatriptan 2.5 mg (n = 75), 5 mg (n = 130), or rizatriptan 10 mg (n = 145). Headache severity, functional disability, and migraine symptoms were measured immediately before dosing (0) and at 0.5, 1, 1.5, 2, 3, and 4 h post-dose. Patients were permitted to take a second dose of test drug at 2 h if their headache pain was moderate or severe (i.e., placebo initially-->rizatriptan 10 mg as optional second dose; rizatriptan 2.5 mg, 5 mg, or 10 mg initially-->placebo as optional second dose). An upward dose-response relationship was observed among placebo, rizatriptan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief, i.e., a change in headache severity to "no pain or mild pain" at 2 h post-dose. The relationship was evident even at the first recorded timepoint, 30 min, and was statistically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain relief was 47.6% for rizatriptan 10 mg; 45.4% for rizatriptan 5 mg; 21.3% for rizatriptan 2.5 mg; and 17.9% for placebo. Seventy percent of patients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2 h post-dose. Rizatriptan 10 mg was consistently more effective than 5 mg, although the differences were not statistically significant. The most frequent clinical adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.

A placebo-controlled trial of L-365,260, a CCKB antagonist, in panic disorder.

The functional role of cholecystokinin in the central nervous system is unknown. The tetra peptide CCK-4 was previously observed to induce panic attacks in a majority of normal volunteers and patients with panic disorder. Furthermore, it had been demonstrated that pretreatment with 10-50 mg of L-365,260, a selective CCKB antagonist, blocked CCK-4 induced panic in patients with panic disorder. Therefore, the present multicenter, placebo-controlled, double-blind trial was designed to investigate the efficacy of L-365,260, a CCKB antagonist, in patients with panic disorder with or without agoraphobia. Following a 1-week, single-blind placebo period, 88 patients were randomized to double-blind treatment in which they received either L-365,260, 30 mg qid, or placebo for 6 weeks. At the dose tested, there were no clinically significant differences between L-365,260 and placebo in global improvement ratings, Hamilton anxiety rating scale scores, panic attack frequency, panic attack intensity, or disability measures. The possible reasons for lack of effect with L-365,260 are discussed.