J Clin Pharmacol
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PHARMACOKINETICS

Evaluation of Safety and Pharmacokinetics of Consecutive Multiple-Day Dosing of Palonosetron in Healthy Subjects

Thomas L. Hunt, MD, PhD, Susan C. Gallagher, MS, Michael T. Cullen, Jr, MD, MBA and Ajit K. Shah, PhD

From PPD Development LLC, Austin, Texas (Dr Hunt), and MGI PHARMA, INC, Bloomington, Minnesota (Ms Gallagher, Dr Cullen, Dr Shah).

This study evaluated the safety and pharmacokinetics of consecutive multiple-day dosing of palonosetron. Sixteen healthy subjects received an intravenous bolus dose of palonosetron 0.25 mg (n = 12) or placebo (n = 4) daily for 3 consecutive days. Safety was evaluated throughout the study. Serial plasma samples were collected on days 1 and 3 for pharmacokinetic determinations. Three days of dosing with palonosetron 0.25 mg was safe and well tolerated. There were no clinically significant changes from baseline in laboratory values, vital signs, physical examinations, or electrocardiogram intervals. Plasma palonosetron concentrations declined in a biphasic manner, measurable up to 168 hours after dosing on day 3. Mean terminal phase elimination half-life after day 3 dosing was 42.8 hours. The 2.1-fold accumulation of palonosetron in plasma following 3 daily doses was predictable based on elimination half-life of approximately 40 hours, and the maximum plasma concentration remained below the maximum plasma concentration previously observed after a single, well-tolerated 0.75 mg intravenous bolus dose of palonosetron.

Key Words: 5-HT3 receptor antagonist • palonosetron • chemotherapy-induced nausea • antiemetic agent • pharmacokinetics

Address for reprints: Ajit K. Shah, PhD, MGI PHARMA, INC, 5775 West Old Shakopee Road, Suite 100, Bloomington, MN 55437-3174.




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A. Shah, T. DeGroot, and G. Apseloff
Pharmacokinetic evaluation and safety profile of a 15-minute versus 30-second infusion of palonosetron in healthy subjects.
J. Clin. Pharmacol., October 1, 2006; 46(10): 1139 - 1145.
[Abstract] [Full Text] [PDF]


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