Establishing the Maximum Tolerated Dose of Lesopitron in Patients With Generalized Anxiety Disorder
Autor: | Jameel Hourani, John J. Sramek, Neal R. Cutler, C.M. Jensen, Fresquet A, Stanford S. Jhee, Martinez L, Bolles K, A.T. Carrington, G. Marion-Landais |
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Rok vydání: | 1996 |
Předmět: |
Adult
Male Lightheadedness Adolescent Nausea medicine.drug_class Anxiolytic Piperazines Buspirone Gepirone Double-Blind Method medicine Humans Pharmacology (medical) Aged Psychiatric Status Rating Scales Azapirone business.industry Lesopitron Middle Aged Anxiety Disorders Psychiatry and Mental health Pyrimidines Anti-Anxiety Agents Tolerability Anesthesia Female medicine.symptom business medicine.drug |
Zdroj: | Journal of Clinical Psychopharmacology. 16:454-458 |
ISSN: | 0271-0749 |
DOI: | 10.1097/00004714-199612000-00009 |
Popis: | Lesopitron, a 5-hydroxytryptamine 1A agonist, is a new potential anxiolytic of the azapirone class. It has greater potency in animal models of anxiety than buspirone, gepirone, or ipsapirone, and it lacks the antidopaminergic effects associated with buspirone. Lesopitron has been tolerated at single doses up to 50 mg and repeated dosages of 45 mg/day in healthy volunteers. Forty-two patients with generalized anxiety disorder (GAD) were enrolled in this double-blind bridging study to determine the safety and tolerability of fixed doses of lesopitron (20, 25, 30, 40, 45, 50, and 60 mg two times a day) over a 6 1/2-day inpatient administration period. Each of the seven panels included six patients (four drug/two placebo). One patient in the 25-mg, two-times-a-day panel voluntarily withdrew because of increased anxiety symptoms. One patient experienced severe orthostatic hypotension at 60 mg two times a day, and moderate to severe adverse events (dizziness, lightheadedness, nausea, headache) occurred in two other patients at this dosage. The most commonly reported adverse events in all the panels were headache, dizziness, and nausea. Lesopitron is rapidly absorbed in patients, having a time to maximum concentration (T max ) ranging from 0.5 to 1 hour, and its elimination half-life ranged from 1.1 to 5.6 hours. Peak plasma concentrations showed high interindividual variability for lesopitron, but increased linearly with dose for the main metabolite, 5-hydroxylesopitron. We defined the maximum tolerated dose in GAD patients as 50 mg two times a day, twice as high as the highest dose tested in healthy volunteers. |
Databáze: | OpenAIRE |
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