Abstract
beta2-glycoprotein I is the best-characterized antigenic target for antiphospholipid autoantibodies. We synthesized a tetrameric conjugate of the domain 1 of beta2-glycoprotein I (LJP 993) aimed at developing the conjugate as a Toleragen to suppress antiphospholipid syndrome. The present studies focused on determining the stability, tissue distribution, plasma concentration-time profile and excretion of the LJP 993 in mice. The stability of LJP 993 in mouse plasma was quantitatively evaluated using strong cation-exchange high performance liquid chromatography. ( 125)I-labeled LJP 993 was intravenously injected to mice, and levels of (125)I-labeled LJP 993 in plasma, tissues, urine and feces were determined at known intervals. Incubation of LJP 993 with mouse serum at 37 degrees C for 8 h resulted in a decrease by 34% of LJP 993 concentration. No degradation fragment was observed during the incubation. After a single intravenous administration of (125)I-LJP 993 (0.5 and 5 mg/kg) to mice, both C(max) and area-under-curve values increased in a dose-proportional manner, and blood radioactivity disappeared in a bi-exponential manner with the distribution half-lives equal to 1.7 min, and the elimination half-lives 188 and 281 min, re...Continue Reading
References
Sep 1, 1979·Kidney International·T MaackD Sigulem
Aug 1, 1992·Journal of Pharmaceutical Sciences·M F PowellS Colón
Dec 17, 1991·Biochemistry·H Kato, K Enjyoji
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·H P McNeilS A Krilis
Sep 1, 1993·Pharmaceutical Research·M F PowellS M Colon
Sep 3, 1998·European Journal of Pharmacology·L Jia, R C Blantz
Nov 14, 1998·Lupus·T KoikeE Matsuura
Nov 14, 1998·Lupus·G M IversonE J Victoria
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·G M IversonD M Marquis
May 29, 1999·Bioconjugate Chemistry·D S JonesE J Victoria
Aug 2, 2001·The Journal of Pharmacy and Pharmacology·L JiaL Yu
Nov 22, 2001·Bioconjugate Chemistry·D S JonesE J Victoria
Sep 21, 2002·Pharmaceutical Research·Lee JiaSteve D Weitman
Dec 18, 2002·Journal of Pharmaceutical Sciences·Lee JiaSteve D Weitman
Sep 30, 2003·Lupus·V StrandUNKNOWN LJP 394 Investigator Consortium
Oct 14, 2003·International Immunopharmacology·Keith A CockerillMary-Ann Campbell
Jul 3, 2004·Lupus·J T Merrill
Sep 21, 2004·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Keith A CockerillMatthew D Linnik
Nov 24, 2006·Lupus·K McElhoneL S Teh
Apr 17, 2007·Lupus·M Haubitz
Sep 18, 2007·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Lee JiaDavid H Munn
Jan 29, 2008·Current Drug Metabolism·Xiaodong Liu, Lee Jia
Jan 29, 2008·Current Drug Metabolism·Lee Jia, Xiaodong Liu