PMID- 12520630
OWN - NLM
STAT- MEDLINE
DCOM- 20030314
LR  - 20190826
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 43
IP  - 1
DP  - 2003 Jan
TI  - Safety and pharmacokinetics of ReN1869: a first human dose study in healthy 
      subjects after single-dose administration.
PG  - 66-73
AB  - ReN1869 (NNC 05-1869) is a novel, selective H1 receptor antagonist that has been 
      developed for analgesic purposes. In a first human dose administration study, the 
      safety and pharmacokinetics of seven single oral doses in the range of 3.5 to 95 
      mg ReN1869 were studied. The study was a randomized, double-blind, 
      placebo-controlled, dose-escalating study in 56 healthy subjects. No serious or 
      severe adverse events were reported. After active doses, an average of 0.6 
      adverse events (AEs) was reported per subject in comparison to 0.5 AEs per 
      subject after placebo, and the frequency of subjects reporting AEs was not 
      related to dose level. The most frequently reported adverse events were 
      dizziness, fatigue, and somnolence, and their occurrence was not proportional to 
      dose. Vital signs, ECG recordings, and clinical laboratory results showed no 
      changes of clinical relevance. During telemetric monitoring at all dose levels 
      until 4 hours after dosing, no clinically relevant abnormalities were observed. A 
      maximally tolerated dose was not identified. ReN1869 was rapidly absorbed after 
      dosing. The overall mean value of t1/2 and oral clearance was 4.7 hours and 11.7 
      L/h, respectively. The parameters Cmax and AUC increased proportionally with dose 
      level, whereas all other pharmacokinetic parameters were independent of the dose. 
      In conclusion, single-dose administration of ReN1869 in doses up to 95 mg 
      exhibited very few adverse events and no clinically relevant effects on any of 
      the observed safety parameters. The pharmacokinetics points to simple first-order 
      pharmacokinetics for ReN1869. All together, it makes ReN1869 a potential new drug 
      candidate for the treatment of chronic pain and inflammatory conditions of 
      neurogenic origin.
FAU - Skrumsager, Birte K
AU  - Skrumsager BK
AD  - Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark.
FAU - Ingwersen, Steen H
AU  - Ingwersen SH
FAU - Gerrits, Mireille
AU  - Gerrits M
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Histamine H1 Antagonists)
RN  - 0 (Piperidines)
RN  - 0 (ReN 1869)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Histamine H1 Antagonists/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Humans
MH  - Male
MH  - Piperidines/administration & dosage/adverse effects/*pharmacokinetics
EDAT- 2003/01/11 04:00
MHDA- 2003/03/15 04:00
CRDT- 2003/01/11 04:00
PHST- 2003/01/11 04:00 [pubmed]
PHST- 2003/03/15 04:00 [medline]
PHST- 2003/01/11 04:00 [entrez]
AID - 10.1177/0091270002239708 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2003 Jan;43(1):66-73. doi: 10.1177/0091270002239708.