PMID- 26648084
OWN - NLM
STAT- MEDLINE
DCOM- 20170117
LR  - 20210109
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 81
IP  - 5
DP  - 2016 May
TI  - Pharmacokinetics and safety of single doses of tabalumab in subjects with 
      rheumatoid arthritis or systemic lupus erythematosus.
PG  - 908-17
LID - 10.1111/bcp.12860 [doi]
AB  - AIMS: Two phase 1 studies evaluated the pharmacokinetics (PK), safety and 
      biological activity of tabalumab, a human monoclonal antibody against B-cell 
      activating factor (BAFF), administered intravenously (i.v.) or subcutaneously 
      (s.c.) in subjects with rheumatoid arthritis (RA) or systemic lupus erythematosus 
      (SLE). METHODS: In study A, subjects with RA (n = 23) or SLE (n = 6) received a 
      single i.v. dose of tabalumab (RA 0.01, 0.04, 0.125, 0.5, 2.0, and 8.0 mg kg(-1) 
      and SLE 0.125 or 2.0 mg kg(-1) ) or placebo. In study B, subjects with RA 
      received a single tabalumab dose i.v. (10 mg) (n = 12) or s.c. (20 mg) (n = 12). 
      Serum tabalumab and CD20+ B cells were evaluated and safety was assessed 
      throughout both studies. RESULTS: Tabalumab PK were non-linear across the 0.01 to 
      8.0 mg kg(-1) dose range. Clearance (CL) decreased from 2.9 to 0.1 l day(-1) and 
      terminal half-life (t1/2 ) increased from about 1.6 to 25 days. Subjects with RA 
      or SLE had similar PK. After s.c. dosing, tabalumab time to maximal concentration 
      (tmax ) was 5.5 days. Absolute bioavailability (F) was approximately 62%. 
      Following tabalumab dosing, CD20+ B cells transiently increased from baseline 
      followed by a progressive decrease below baseline. CONCLUSION: A single tabalumab 
      dose administered i.v. or s.c. was well tolerated and had non-linear CL over the 
      dose range investigated in subjects with RA and SLE. The non-linearity likely 
      reflects target-mediated CL due to binding to BAFF. Tabalumab showed biological 
      activity based on changes in peripheral CD20+ lymphocyte numbers in both subjects 
      with RA and SLE.
CI  - (c) 2015 The British Pharmacological Society.
FAU - Witcher, Jennifer
AU  - Witcher J
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Fleischmann, Roy
AU  - Fleischmann R
AD  - Metroplex Clinical Research Center, Dallas, Texas.
FAU - Chindalore, Vishala L
AU  - Chindalore VL
AD  - Pinnacle Research Group, Anniston, Alabama, USA.
FAU - Hansen, Ryan J
AU  - Hansen RJ
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Hu, Leijun
AU  - Hu L
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Radtke, David
AU  - Radtke D
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Voelker, James
AU  - Voelker J
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Gomez, Elisa
AU  - Gomez E
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - McColm, Juliet
AU  - McColm J
AD  - Eli Lilly and Company, Windlesham, UK.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160225
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antigens, CD20)
RN  - 0 (B-Cell Activating Factor)
RN  - 0 (TNFSF13B protein, human)
RN  - PQP8VH3MJW (tabalumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/administration & dosage/adverse effects/*pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Antigens, CD20/immunology
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - B-Cell Activating Factor/*antagonists & inhibitors
MH  - B-Lymphocyte Subsets/drug effects/immunology
MH  - Female
MH  - Humans
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Lupus Erythematosus, Systemic/*drug therapy
MH  - Male
MH  - Middle Aged
PMC - PMC4834597
OTO - NOTNLM
OT  - B-cell activating factor
OT  - pharmacokinetics
OT  - rheumatoid arthritis
OT  - systemic lupus erythematosus
OT  - tabalumab
EDAT- 2015/12/10 06:00
MHDA- 2017/01/18 06:00
PMCR- 2017/05/01
CRDT- 2015/12/10 06:00
PHST- 2015/04/30 00:00 [received]
PHST- 2015/11/24 00:00 [revised]
PHST- 2015/12/06 00:00 [accepted]
PHST- 2015/12/10 06:00 [entrez]
PHST- 2015/12/10 06:00 [pubmed]
PHST- 2017/01/18 06:00 [medline]
PHST- 2017/05/01 00:00 [pmc-release]
AID - BCP12860 [pii]
AID - 10.1111/bcp.12860 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2016 May;81(5):908-17. doi: 10.1111/bcp.12860. Epub 2016 Feb 
      25.