PMID- 28636184
OWN - NLM
STAT- MEDLINE
DCOM- 20180521
LR  - 20220331
IS  - 1755-5922 (Electronic)
IS  - 1755-5914 (Linking)
VI  - 35
IP  - 5
DP  - 2017 Oct
TI  - Pharmacokinetics and pharmacodynamics of bococizumab, a monoclonal antibody to 
      PCSK9, after single subcutaneous injection at three sites [NCT 02043301].
LID - 10.1111/1755-5922.12278 [doi]
AB  - AIM: To characterize the single-dose pharmacokinetics (PK) and pharmacodynamics 
      (PD) of bococizumab, a monoclonal antibody inhibiting proprotein convertase 
      subtilisin/kexin type 9 (PCSK9), administered subcutaneously (s.c.) to the 
      abdomen, thigh, or upper arm (NCT02043301). METHODS: Seventy-five adults with 
      low-density lipoprotein cholesterol (LDL-C) >/=130 mg/dL and not on background 
      lipid-lowering therapy were randomized (1:1:1) to a single 150-mg s.c. dose of 
      bococizumab administered to the abdomen, thigh, or upper arm. Blood samples for 
      bococizumab and lipids were collected for 12 weeks postdose. RESULTS: Plasma 
      bococizumab concentration-time profiles and PK parameters were generally similar 
      across injection sites. Mean maximum observed concentration (C(max) ) ranged from 
      8.14 to 11.9 mug/mL, and area under the concentration-time curve (AUC(inf) ) 
      ranged from 160.3 to 198.9 microg∙day/mL. The median time to C(max) (T(max) ) ranged 
      from 4.25 to 6.93 days. Similar LDL-C concentration-time profiles were observed 
      across injection sites, with mean (% coefficient of variation) maximum reductions 
      in LDL-C of -57.5% (15.8), -57.0% (25.9), and -55.0% (24.1) for the abdomen, 
      thigh, and upper arm, respectively. Adverse events (AEs) were mostly mild and 
      generally similar across injection sites. Commonly reported AEs were upper 
      respiratory tract infection (9.3%), headache (6.7%), and injection site reaction 
      (6.7%). One serious AE was reported (ischemic colitis), which was not considered 
      related to study drug. CONCLUSIONS: Similar PK profiles and robust LDL-C 
      reductions were observed following a single 150-mg s.c. injection of bococizumab 
      administered to the abdomen, thigh, or upper arm in untreated subjects with LDL-C 
      >/=130 mg/dL. Bococizumab was generally well tolerated following a single 150-mg 
      s.c. administration in this subject population.
CI  - (c) 2017 John Wiley & Sons Ltd.
FAU - Wang, Ellen Q
AU  - Wang EQ
AD  - Clinical Pharmacology, Global Product Development, Pfizer Inc, New York, NY, USA.
FAU - Plotka, Anna
AU  - Plotka A
AD  - Global Biometrics and Data Management, Global Product Development, Pfizer Inc, 
      Collegeville, PA, USA.
FAU - Salageanu, Joanne
AU  - Salageanu J
AD  - Clinical Pharmacology, Global Product Development, Pfizer Inc, Groton, CT, USA.
FAU - Sattler, Catherine
AU  - Sattler C
AD  - Clinical Sciences and Operations, Global Product Development, Pfizer Inc, Groton, 
      CT, USA.
FAU - Yunis, Carla
AU  - Yunis C
AD  - Global Product Development CVMET Therapeutics, Pfizer Inc, New York, NY, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02043301
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - England
TA  - Cardiovasc Ther
JT  - Cardiovascular therapeutics
JID - 101319630
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (PCSK9 Inhibitors)
RN  - 45M75JVK38 (bococizumab)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
SB  - IM
MH  - Abdomen
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Anticholesteremic Agents/*administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Biomarkers/blood
MH  - Cholesterol, LDL/*blood
MH  - Down-Regulation
MH  - Dyslipidemias/blood/diagnosis/*drug therapy/epidemiology
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - *PCSK9 Inhibitors
MH  - Proprotein Convertase 9/immunology/metabolism
MH  - Thigh
MH  - Treatment Outcome
MH  - United States
MH  - Upper Extremity
OTO - NOTNLM
OT  - Bococizumab
OT  - Injection site
OT  - LDL-C
OT  - Pharmacokinetics
OT  - Relative bioavailability
EDAT- 2017/06/22 06:00
MHDA- 2018/05/22 06:00
CRDT- 2017/06/22 06:00
PHST- 2017/02/08 00:00 [received]
PHST- 2017/06/09 00:00 [revised]
PHST- 2017/06/15 00:00 [accepted]
PHST- 2017/06/22 06:00 [pubmed]
PHST- 2018/05/22 06:00 [medline]
PHST- 2017/06/22 06:00 [entrez]
AID - 10.1111/1755-5922.12278 [doi]
PST - ppublish
SO  - Cardiovasc Ther. 2017 Oct;35(5). doi: 10.1111/1755-5922.12278.