The pharmacokinetics of interleukin-1 receptor antagonist in Chinese subjects with rheumatoid arthritis.
To characterize the pharmacokinetic (PK) profile of interleukin-1 receptor antagonist (IL-1ra) after a single injection, and to assess the safety and tolerability of IL-1ra, a total of 15 adult Chinese subjects with rheumatoid arthritis (RA) were enrolled into this study. Study medication was administered on day 1. Blood samples for PK testing were collected predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 h postdose. Adverse events data was collected and monitored throughout the study. Plasma IL-1ra concentrations were measured by enzyme-linked immunosorbent assay. Individual IL-1ra PK parameters were estimated by noncompartmental analysis. After subcutaneous (s.c.) injection of 1mg/kg IL-1ra, the T(max) was reached at 2-6h postdose. The mean (S.D.) of C(max) was 687 ng/ml (197 ng/ml). Plasma concentration subsequently declined with a mean (S.D.) of T(1/2) value of 3.76 h (1h). The mean (S.D.) of plasma clearance after administration value was 150 ml/min (52.1 ml/min). No deleterious effects, serious adverse events, or withdrawals due to adverse events occurred during this study. The PK parameters for Chinese subjects with RA were comparable to those for non-Chinese subjects with RA. IL-1ra was well tolerated during this study, and no significant safety concerns were identified after administration.
Chang
Deh-Ming
DM
Rheumatology/Immunology/Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 325, Cheng-Kung Road, Section 2, Neihu 114, Taipei, Taiwan, ROC. ming0503@ms3.hinet.net
Chang
Sun-Yran
SY
Yeh
Ming-Kung
MK
Lai
Jenn-Huang
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D044466:Asian People; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012795:Sialoglycoproteins / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins