PMID- 15102873
OWN - NLM
STAT- MEDLINE
DCOM- 20041216
LR  - 20221207
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 44
IP  - 5
DP  - 2004 May
TI  - Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 
      receptor antagonist, in U.S. and Japanese healthy subjects.
PG  - 520-31
AB  - Palonosetron (Aloxi, Onicit) is a selective 5-HT(3) receptor antagonist recently 
      approved by the Food and Drug Administration for the prevention of acute and 
      delayed chemotherapy-induced nausea and vomiting. This study was performed to 
      determine the pharmacokinetics and assess the safety and tolerability of 
      intravenous (IV) palonosetron in healthy U.S. and Japanese subjects. Subjects 
      were administered a single IV dose of palonosetron, ranging from 0.3 to 90 
      microg/kg in either of two randomized, double-blind, placebo-controlled, 
      ascending-dose studies (n = 80 and n = 32, respectively). Serial blood samples 
      were obtained in both studies to evaluate the pharmacokinetics of palonosetron 
      and its N-oxide metabolite, M9. Intravenous palonosetron was well tolerated 
      across a wide range of doses in both studies. The incidence and severity of 
      adverse events (AEs) were similar between subjects receiving palonosetron and 
      those receiving placebo, with no dose-dependent incidences. The most frequently 
      reported AEs were headache, transient elevation of liver enzymes, and 
      constipation. Systemic exposure (AUC and C(max)) for palonosetron generally 
      increased with increasing dose. Mean total body clearance, elimination half-life, 
      and apparent volume of distribution ranged from 1.11 to 3.90 mL/min/kg, 33.7 to 
      54.1 hours, and 3.85 to 12.6 L/kg, respectively, in U.S. subjects and from 2.58 
      to 3.50 mL/min/kg, 30.8 to 36.8 hours, and 6.96 to 9.85 L/kg, respectively, in 
      Japanese subjects. The pharmacokinetics of palonosetron appeared to be 
      independent of dose, with no dose adjustment required in Japanese subjects. The 
      plasma concentration profile of palonosetron, as represented by a half-life of 
      approximately 40 hours, may provide a clinical advantage over other 5-HT(3) 
      antagonists.
FAU - Stoltz, Randall
AU  - Stoltz R
AD  - GFI Pharmaceutical Services, Evansville, Indiana, USA.
FAU - Cyong, Jong-Chol
AU  - Cyong JC
FAU - Shah, Ajit
AU  - Shah A
FAU - Parisi, Simona
AU  - Parisi S
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Isoquinolines)
RN  - 0 (Quinuclidines)
RN  - 0 (Receptors, Serotonin, 5-HT3)
RN  - 0 (Serotonin 5-HT3 Receptor Antagonists)
RN  - 5D06587D6R (Palonosetron)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - *Asian People
MH  - Constipation/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Headache/chemically induced
MH  - Humans
MH  - Inactivation, Metabolic/physiology
MH  - Infusions, Intravenous
MH  - Injections, Intravenous
MH  - Isoquinolines/adverse effects/metabolism/*pharmacokinetics
MH  - Liver/drug effects/enzymology
MH  - Men
MH  - Palonosetron
MH  - Quinuclidines/adverse effects/metabolism/*pharmacokinetics
MH  - Receptors, Serotonin, 5-HT3/*administration & dosage
MH  - *Serotonin 5-HT3 Receptor Antagonists
MH  - Time Factors
MH  - United States
EDAT- 2004/04/23 05:00
MHDA- 2004/12/17 09:00
CRDT- 2004/04/23 05:00
PHST- 2004/04/23 05:00 [pubmed]
PHST- 2004/12/17 09:00 [medline]
PHST- 2004/04/23 05:00 [entrez]
AID - 44/5/520 [pii]
AID - 10.1177/0091270004264641 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2004 May;44(5):520-31. doi: 10.1177/0091270004264641.