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A Double‐Blind, Placebo‐Controlled, Dose‐Ranging Safety Evaluation of Single‐Dose Intravenous Dolasetron in Healthy Male Volunteers
Author(s) -
Hunt Thomas L.,
Cramer Michael,
Shah Ajit,
Stewart William,
Benedict Claude R.,
Hahne William F.
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.tb04111.x
Subject(s) - medicine , placebo , lightheadedness , anesthesia , tolerability , adverse effect , retching , nausea , dose ranging study , antiemetic , vomiting , double blind , alternative medicine , pathology
The safety and tolerability of dolasetron mesylate, a potent and selective 5‐HT 3 receptor antagonist, were evaluated after single intravenous doses in healthy male volunteers. In this double‐blind, placebo‐controlled, randomized, phase I study, 80 subjects received either placebo or dolasetron in escalating doses (0.6 to 5.0 mg/k). Subjects were monitored for adverse events, vital sign and laboratory alterations, and changes in electrocardiographic (ECG) intervals and electroencephalographs (EEG) patterns. Overall, the percentage of subjects reporting adverse events was similar in those receiving dolasetron (44/64; 68.8%) or placebo (10/16; 62.5%); most adverse events were mild in severity. Subjects receiving dolasetron reported a higher incidence of central nervous system (headache and dizziness/lightheadedness), gastrointestinal (increased appetite and nausea), and visual adverse events and taste alterations. No clinically significant changes in laboratory variables were observed. Transient and asymptomatic ECG changes (small mean increases in PR interval and QRS complex duration versus baseline) were noted in several subjects at 1 to 2 hours after infusion at doses ≥ 3.0 mg/kg. Transient, mild blood pressure decreases were observed in five subjects, including one on placebo. Dolasetron mesylate was well tolerated in single intravenous doses up to 5.0 mg/kg in healthy male volunteers. Clinical studies of the drug are ongoing for antiemetic indications.