PMID- 19743503
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20181211
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Linking)
VI  - 99
IP  - 1
DP  - 2010 Jan
TI  - Pharmacokinetics and immunoglobulin response of subcutaneous and intravenous 
      atacicept in patients with systemic lupus erythematosus.
PG  - 524-38
LID - 10.1002/jps.21839 [doi]
AB  - Atacicept, a recombinant fusion protein of the TACI receptor and human IgG, is an 
      inhibitor of B-Lymphocyte Stimulator (BLyS) and APRIL, potent stimulators of B 
      cell maturation, proliferation, and survival. Pharmacokinetics (PKs) and 
      biological activity of intravenous (iv) and subcutaneous (sc) atacicept are 
      described here for patients with systemic lupus erythematosus in two randomized, 
      double-blind, placebo-controlled, Phase Ib studies. Study 1: Six cohorts of eight 
      patients received sc atacicept (single dose: 0.3, 1, 3, or 9 mg/kg; four weekly 
      doses: 1 or 3 mg/kg), or placebo (3:1 ratio). Study 2: Four cohorts of six 
      patients received iv atacicept (single dose: 3, 9, or 18 mg/kg; multiple dose: 2 
      x 9 mg/kg), or matching placebo (5:1 ratio). PK profiles were determined through 
      serum atacicept and atacicept-BLyS complex, and biological activity through IgA, 
      IgG, and IgM levels. PK profiles of atacicept were influenced by saturable 
      binding between atacicept and its ligands, and were consistent and predictable 
      across doses and regimens. Atacicept's biological activity was compatible with 
      its presumed mechanism of action. Bioavailability was approximately 30-40% 
      following sc or iv administration and similar doses yielded similar biological 
      activity irrespective of administration route. This observation may have a 
      mechanistic foundation and may inform dosing regimen design for future studies.
FAU - Nestorov, I
AU  - Nestorov I
AD  - ZymoGenetics, 1201 Eastlake Avenue East, Seattle, Washington 98102, USA.
FAU - Papasouliotis, O
AU  - Papasouliotis O
FAU - Pena Rossi, C
AU  - Pena Rossi C
FAU - Munafo, A
AU  - Munafo A
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Biomarkers)
RN  - 0 (Immunoglobulins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - K3D9A0ICQ3 (TACI receptor-IgG Fc fragment fusion protein)
SB  - IM
MH  - Adult
MH  - Biomarkers/blood
MH  - Cohort Studies
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Immunoglobulins/*blood
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Lupus Erythematosus, Systemic/blood/*drug therapy/immunology
MH  - Male
MH  - Middle Aged
MH  - Recombinant Fusion Proteins/administration & 
      dosage/*pharmacokinetics/pharmacology/therapeutic use
MH  - Young Adult
EDAT- 2009/09/11 06:00
MHDA- 2010/11/17 06:00
CRDT- 2009/09/11 06:00
PHST- 2009/09/11 06:00 [entrez]
PHST- 2009/09/11 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
AID - S0022-3549(16)30333-1 [pii]
AID - 10.1002/jps.21839 [doi]
PST - ppublish
SO  - J Pharm Sci. 2010 Jan;99(1):524-38. doi: 10.1002/jps.21839.