The comparability of etanercept pharmacokinetics in healthy Japanese and American subjects.
Thirty Japanese (J) and 32 American (A) healthy subjects received single doses of etanercept by subcutaneous injection, in 3 separate trials. Serum samples were collected for 480 hours after dosing. Concentrations were determined using enzyme-linked immunosorbent assay methods. Pharmacokinetic parameters were calculated using both non-compartmental and compartmental methods. Etanercept was slowly absorbed, with mean+/-SD time to maximum serum concentration of 47+/-15 hours (J), and 51+/-20 hours (A). The maximum serum concentration and area under the concentration time curve increased for doses 10 mg, 25 mg, and 50 mg, in a linear relationship. Etanercept was slowly eliminated, with observed mean+/-SD half-life of 80+/-25 hours (J) and 75+/-15 hours (A) and mean+/-SD apparent clearance of 144+/-65 mL/h (J) and 132+/-74 mL/h (A). Very low concentrations of etanercept were observed in the urine samples collected in the Japanese subjects. All adverse reactions observed resolved without issue, and none required discontinuation from the study.
Division of Rheumatology, Department of Medicine, Toho University School of Medicine, and the Sekino Clinical Pharmacology Clinic, Tokyo, Japan.
Shinichi
S
Kawai
Hisayuki
H
Sekino
Noriaki
N
Yamashita
Shinichi
S
Tsuchiwata
Hanjui
H
Liu
Joan M
JM
Korth-Bradley
D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007279:Injections, Subcutaneous; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016037:Single-Blind Method; D014481:United States; D044465:White People
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D000068800:Etanercept