PMID- 23547848
OWN - NLM
STAT- MEDLINE
DCOM- 20130806
LR  - 20210224
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 51
IP  - 6
DP  - 2013 Jun
TI  - Pharmacokinetics and pharmacodynamics of tocilizumab, a humanized 
      anti-interleukin-6 receptor monoclonal antibody, following single-dose 
      administration by subcutaneous and intravenous routes to healthy subjects.
PG  - 443-55
LID - 10.5414/CP201819 [doi]
AB  - OBJECTIVES: Tocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) 
      monoclonal antibody, given by intravenous (i.v.) infusion every 4 weeks has been 
      approved for treatment of patients with rheumatoid arthritis. The objective of 
      the study was to determine pharmacokinetics (PK) and pharmacodynamics (PD) of 
      tocilizumab including absolute PK and PD bioavailabilities following subcutaneous 
      (s.c.) administration. METHODS: The PK and PD of tocilizumab 162 mg or 81 mg 
      after single s.c. and i.v. administration were evaluated in an open-label, 
      4-parallel group study involving 48 healthy subjects (n = 12/group). RESULTS: 
      Following single-dose s.c. administration of tocilizumab, area under the serum 
      concentration-time curve (AUCinfinity) increased by 6.4-fold, and maximum serum 
      concentration (Cmax) increased by 4-fold, as the dose was doubled from 81 mg to 
      162 mg. Tocilizumab absolute PK bioavailability (AUCinfinity ratio (s.c./i.v.)) was 
      higher at 162 mg (48.8%) than at 81 mg (22.7%). Tocilizumab PD bioavailability 
      for soluble IL-6R (sIL-6R) (AUClast ratio (s.c./i.v.)) was 109% at 162 mg and 
      80.9% at 81 mg. Tocilizumab PD bioavailability for C-reactive protein (CRP) 
      effect was 98.2% (CRP AUC480h ratio) at 162 mg and 80.4% (AUC240h ratio 
      (s.c./i.v.)) at 81 mg. Tocilizumab was well tolerated at both doses after s.c. 
      and i.v. administration. CONCLUSIONS: Tocilizumab absolute PK bioavailability for 
      s.c. vs. i.v. administration was low; however, the PD effects for sIL-6R and CRP 
      levels were comparable after 162-mg s.c. and i.v. administration. Therefore, 162 
      mg s.c. dose is a comparable dose for 162 mg i.v. dose based on PD 
      bioavailability.
FAU - Zhang, Xiaoping
AU  - Zhang X
AD  - Department of Clinical Pharmacology, Hoffmann-La Roche Inc., Nutley, NJ, USA. 
      zhangxiaoping@aol.com
FAU - Georgy, Angela
AU  - Georgy A
FAU - Rowell, Lucy
AU  - Rowell L
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-6)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - I031V2H011 (tocilizumab)
SB  - IM
CIN - J Med Virol. 2021 Jan;93(1):69-70. PMID: 32492210
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/*pharmacokinetics/*pharmacology
MH  - Biological Availability
MH  - C-Reactive Protein/analysis
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Subcutaneous
MH  - Interleukin-6/*blood
MH  - Male
MH  - Middle Aged
MH  - Receptors, Interleukin-6/*antagonists & inhibitors
MH  - Time Factors
MH  - Young Adult
EDAT- 2013/04/04 06:00
MHDA- 2013/08/07 06:00
CRDT- 2013/04/04 06:00
PHST- 2013/05/29 00:00 [accepted]
PHST- 2013/04/04 06:00 [entrez]
PHST- 2013/04/04 06:00 [pubmed]
PHST- 2013/08/07 06:00 [medline]
AID - 10539 [pii]
AID - 10.5414/CP201819 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2013 Jun;51(6):443-55. doi: 10.5414/CP201819.