PMID- 15386478
OWN - NLM
STAT- MEDLINE
DCOM- 20050114
LR  - 20171116
IS  - 0142-2782 (Print)
IS  - 0142-2782 (Linking)
VI  - 25
IP  - 7
DP  - 2004 Oct
TI  - A multiple-dose, safety, tolerability, pharmacokinetics and pharmacodynamic study 
      of oral recombinant human interleukin-11 (oprelvekin).
PG  - 291-6
AB  - A study in healthy men and women was performed to assess the safety, 
      tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally 
      administered recombinant human interleukin-11 (oprelvekin) (OAO). Four cohorts of 
      10 subjects each received 3, 5, 10 or 30 mg (8:2/OAO:placebo ratio), first as a 
      single dose with a 7-day washout period, then 7 consecutive daily doses. Safety 
      was assessed by ongoing evaluation of adverse events (AEs) and laboratory values. 
      PK samples were collected on the first and last day of dose administration. The 
      established effects of subcutaneous oprelvekin on C-reactive protein (CRP, upward 
      arrow), platelet count (upward arrow), fibrinogen (upward arrow) and hemoglobin 
      (downward arrow), were evaluated. PK analysis showed that most subjects (27/34, 
      79%) had undetectable serum levels of IL-11. PD measures showed no changes from 
      baseline between any OAO group and the placebo group. Orally administered 
      oprelvekin was safe and well tolerated at all doses. A total of five AEs 
      (abdominal pain, diarrhea, headache, rhinitis, grade 3 alanine aminotransferase 
      elevation) were reported across all groups. Evaluations of serum IL-11 levels 
      indicate that OAO is not systemically absorbed at levels above the lower limit of 
      the bioanalytic assay. These data in addition to the lack of effect on PD 
      measures suggest that there is a decreased potential of systemic adverse events 
      with OAO.
CI  - Copyright (c) 2004 John Wiley & Sons, Ltd.
FAU - Cotreau, Monette M
AU  - Cotreau MM
AD  - Experimental Medicine, Wyeth Research, Cambridge, MA 02140, USA. 
      mcotreau@wyeth.com
FAU - Stonis, Lucille
AU  - Stonis L
FAU - Strahs, Andrew
AU  - Strahs A
FAU - Schwertschlag, Ullrich S
AU  - Schwertschlag US
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - England
TA  - Biopharm Drug Dispos
JT  - Biopharmaceutics & drug disposition
JID - 7911226
RN  - 0 (Interleukin-11)
RN  - 0 (Recombinant Proteins)
RN  - HM5641GA6F (oprelvekin)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Humans
MH  - Interleukin-11/adverse effects/*pharmacokinetics/pharmacology
MH  - Middle Aged
MH  - Recombinant Proteins/adverse effects/*pharmacokinetics/pharmacology
EDAT- 2004/09/24 05:00
MHDA- 2005/01/15 09:00
CRDT- 2004/09/24 05:00
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2005/01/15 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - 10.1002/bdd.415 [doi]
PST - ppublish
SO  - Biopharm Drug Dispos. 2004 Oct;25(7):291-6. doi: 10.1002/bdd.415.