Subcutaneous bioavailability of golimumab at 3 different injection sites in healthy subjects.
This study characterized the pharmacokinetics (PK) of golimumab, an antitumor necrosis factor alpha human IgG1kappa monoclonal antibody, after a single intravenous (IV) or subcutaneous (SC) administration in healthy subjects and determined the absolute bioavailability of SC golimumab delivered at 3 different anatomical regions. Seventy-eight healthy adult males were randomly assigned to receive a single dose of golimumab 100 mg by IV (30-minute infusion, n = 23) or SC administration at different sites (upper arm, n = 18; abdomen, n = 18; thigh, n = 19). Serial blood samples were collected for PK characterization. Following IV administration, the mean maximum observed serum golimumab concentration (C(max)) and the mean area under the concentration versus time curves from time zero to infinity (AUC(0-infinity)) were 29.5 +/- 5.8 microg/mL and 195.9 +/- 48.9 microg x d/mL, respectively. After SC administration, the mean values of C(max) and AUC(0-infinity) were 6.3 +/- 2.8 microg/mL and 100.1 +/- 29.2 microg x d/mL, respectively. The median terminal half-life was similar for SC and IV administration (10.9 and 11.8 days, respectively). The overall mean bioavailability of SC golimumab was 51%, and absorption was similar for the 3 injection sites. Golimumab 100 mg was generally well tolerated in this study. Results support the flexibility in the choice of an injection site for SC administration of golimumab.
Xu
Zhenhua
Z
Centocor Research and Development Inc, Malvern, PA 19355, USA.
Wang
Qingmin
Q
Zhuang
Yanli
Y
Frederick
Bart
B
Yan
Hong
H
Bouman-Thio
Esther
E
Marini
Joseph C
JC
Keen
Monica
M
Snead
David
D
Davis
Hugh M
HM
Zhou
Honghui
H
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007118:Immunoassay; D007074:Immunoglobulin G / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007262:Infusions, Intravenous / Q000379:methods; D007279:Injections, Subcutaneous / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012016:Reference Values; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab