Lack of racial differences in the pharmacokinetics of subcutaneous golimumab in healthy Japanese and Caucasian male subjects.
This phase 1 study evaluated the single-dose pharmacokinetics and safety of subcutaneous golimumab, a human anti-tumor necrosis factor-alpha monoclonal antibody, in healthy Japanese and Caucasian subjects. Eligible subjects were males, aged 20 to 45 years, weighing 50 to 90 kg with a body mass index of 19 to 30 kg/m(2). Japanese and Caucasian subjects were matched by body weight and dose group. Blood samples were collected through day 50 following a single subcutaneous injection of golimumab 50 or 100 mg. The pharmacokinetic parameters were determined using a noncompartmental method. All 51 subjects (24 Japanese, 27 Caucasian) were included in the safety analysis; 47 completed the study and were included in the pharmacokinetic analysis. The pharmacokinetics of golimumab were comparable in both race groups. Peak concentrations were observed approximately 4 to 6 days after administration. No significant differences in exposure or mean half-life (range, 11-13 days) were observed between Japanese and Caucasian subjects at the same dose level. Regardless of race, serum golimumab exposure increased with increasing dose. Mean apparent clearance ranged from 12 to 19 mL/kg/d. Mean apparent volume of distribution (224-262 mL/kg) remained constant with an increase in dose. No antibodies to golimumab were detected. Single subcutaneous injections of golimumab 50 mg or 100 mg were generally well tolerated in these healthy male Japanese and Caucasian subjects.
Pharmacokinetics, Modeling & Simulation, Clinical Pharmacology Sciences, Centocor Research and Development, Inc, C-4-5, 200 Great Valley Parkway, Malvern, PA 19355, USA. jling@its.jnj.com
Jie
J
Ling
Sally
S
Lyn
Zhenhua
Z
Xu
Meguru
M
Achira
Esther
E
Bouman-Thio
Akira
A
Shishido
Joyce
J
Ford
Gopi
G
Shankar
Carrie
C
Wagner
Kenneth T
KT
Kim
Hugh M
HM
Davis
Honghui
H
Zhou
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000906:Antibodies / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001219:Aspartate Aminotransferases / Q000097:blood; D015992:Body Mass Index; D015331:Cohort Studies; D005006:Ethnicity; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D007564:Japan; D008297:Male; D016037:Single-Blind Method; D044465:White People; D055815:Young Adult
D000906:Antibodies; D000911:Antibodies, Monoclonal; C529000:golimumab; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase