PMID- 33386423
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20210623
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 87
IP  - 3
DP  - 2021 Mar
TI  - A phase 1 pharmacokinetic study of oral NEPA, the fixed combination of netupitant 
      and palonosetron, in Chinese healthy volunteers.
PG  - 387-396
LID - 10.1007/s00280-020-04200-2 [doi]
AB  - PURPOSE: Oral NEPA, the only fixed-combination antiemetic, is composed of the 
      neurokinin-1 receptor antagonist netupitant (300 mg) and the 
      5-hydroxytryptamine-3 receptor antagonist palonosetron (0.50 mg). This study was 
      conducted to evaluate the pharmacokinetic profile of netupitant and its main 
      metabolites M1 and M3, and palonosetron in Chinese subjects. Oral NEPA 
      tolerability and safety were also analyzed. METHODS: This was a single-center, 
      single-dose phase 1 study in healthy, adult Chinese volunteers. Eligible subjects 
      received oral NEPA, and blood samples were collected on day 1 predose and at 
      various time points up until day 10 postdose. Pharmacokinetic parameters were 
      analyzed using noncompartmental methods. For safety assessments, adverse events 
      (AEs) were monitored during the study. RESULTS: In total 18 Chinese healthy 
      volunteers received oral NEPA. Netupitant mean maximum plasma concentration 
      (C(max)) [+/- standard deviation] of 698 +/- 217 ng/mL was reached at 3-6 h, with a 
      mean total exposure (AUC(0-inf)) of 22,000 +/- 4410 h.ng/mL. For palonosetron, a 
      mean C(max) of 1.8 +/- 0.252 ng/mL was reached at 2-6 h postadministration, with a 
      mean AUC(0-inf) of 81.0 +/- 14.0 h.ng/mL. The most common treatment-related AEs 
      in > 2 subjects were constipation (n = 9) and tiredness (n = 3). No severe AEs 
      were observed, and no subject withdrew due to AEs. CONCLUSION: Following 
      single-dose administration of oral NEPA in Chinese subjects, the pharmacokinetic 
      profiles of the NEPA components were mostly similar to those reported previously 
      in Caucasians. NEPA was well tolerated with a safety profile in line with that 
      observed in pivotal trials in Caucasians.
FAU - Chen, Rui
AU  - Chen R
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Wang, Hongyun
AU  - Wang H
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Zhong, Wen
AU  - Zhong W
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Chessari, Salvatore
AU  - Chessari S
AD  - Scientific Operations Division, Helsinn Healthcare SA, Lugano, Switzerland.
FAU - Lanzarotti, Corinna
AU  - Lanzarotti C
AD  - Scientific Operations Division, Helsinn Healthcare SA, Lugano, Switzerland.
FAU - Bernareggi, Alberto
AU  - Bernareggi A
AD  - Scientific Operations Division, Helsinn Healthcare SA, Lugano, Switzerland.
FAU - Hu, Pei
AU  - Hu P
AUID- ORCID: 0000-0002-7727-4902
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China. hubei01_pumch@163.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210102
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antiemetics)
RN  - 0 (Drug Combinations)
RN  - 0 (Isoquinolines)
RN  - 0 (Neurokinin-1 Receptor Antagonists)
RN  - 0 (Pyridines)
RN  - 0 (Quinuclidines)
RN  - 0 (Serotonin 5-HT3 Receptor Antagonists)
RN  - 0 (netupitant, palosentron drug combination)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Antiemetics/*administration & dosage/adverse effects/pharmacokinetics
MH  - Area Under Curve
MH  - China
MH  - Drug Combinations
MH  - Female
MH  - Humans
MH  - Isoquinolines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Male
MH  - Neurokinin-1 Receptor Antagonists/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Pyridines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Quinuclidines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Serotonin 5-HT3 Receptor Antagonists/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Young Adult
OTO - NOTNLM
OT  - Antiemetic
OT  - China
OT  - NEPA
OT  - Netupitant
OT  - Palonosetron
OT  - Pharmacokinetics
EDAT- 2021/01/03 06:00
MHDA- 2021/06/24 06:00
CRDT- 2021/01/02 05:18
PHST- 2020/07/07 00:00 [received]
PHST- 2020/11/03 00:00 [accepted]
PHST- 2021/01/03 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2021/01/02 05:18 [entrez]
AID - 10.1007/s00280-020-04200-2 [pii]
AID - 10.1007/s00280-020-04200-2 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2021 Mar;87(3):387-396. doi: 
      10.1007/s00280-020-04200-2. Epub 2021 Jan 2.