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The Safety and Tolerance of Xanomeline Tartrate in Patients with Alzheimer's Disease
Author(s) -
Sramek John J.,
Hurley Daniel J.,
Wardle Thomas S.,
Satterwhite Julie H.,
Hourani Jameel,
Dies Federico,
Cutler Neal R.
Publication year - 1995
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1995.tb04123.x
Subject(s) - dose , placebo , tolerability , medicine , discontinuation , adverse effect , muscarinic agonist , anesthesia , pharmacology , gastroenterology , agonist , receptor , pathology , alternative medicine
Xanomeline tartrate (active ingredient xanomeline) is a muscarinic agonist that has demonstrated specificity for the M 1 receptor in preclinical studies and has been well tolerated at dosages up to 50 mg three times a day in healthy elderly subjects. To define the maximum tolerated dose (MTD) of xanomeline tartrate in patients with Alzheimer's disease, 48 patients (20 men, 28 women) with probable Alzheimer's disease were enrolled in a double‐blind, placebo‐controlled inpatient study to determine the safety and tolerability of 8 fixed dosages of xanomeline tartrate (25, 35, 50, 60, 75, 90, 100, and 115 mg, all three times a day) given for 7 days. For each dosage the treatment panel consisted of six patients (four taking xanomeline tartrate and two taking placebo). With the discontinuation of two patients because of severe intolerable adverse events, a minimum intolerated dose was reached at 115 mg three times a day, and 100 mg three times a day was defined as the MTD. This MTD in patients was two‐fold greater than the MTD previously determined in healthy elderly volunteers.