Evaluation of safety and pharmacokinetics of consecutive multiple-day dosing of palonosetron in healthy subjects.
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.
Hunt
Thomas L
TL
PPD Development LLC, Austin, Texas, USA.
Gallagher
Susan C
SC
Cullen
Michael T
MT
Shah
Ajit K
AK
D000328:Adult; D000932:Antiemetics / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D000077924:Palonosetron; D011812:Quinuclidines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D000932:Antiemetics; D007546:Isoquinolines; D011812:Quinuclidines; D000077924:Palonosetron