Preparation of antibodies against a novel immunosuppressant, FTY720, and development of an enzyme immunoassay for FTY720.
FTY720 (1) is a novel immunosuppressant (immunomodulator), derived from ISP-I (2: myriocin and thermozymocidin). To clarify the pharmacokinetic properties of 1, antibodies against 1 were prepared and a competitive enzyme immunoassay (EIA) was developed. Two kinds of haptens, 3 and 4, for 1 were synthesized and coupled to ovalbumin (OVA). Rabbits were immunized with 3-OVA or 4-OVA, and corresponding antibodies were obtained. Both antibodies recognized the 2-amino-2-(2-phenylethyl)propane-1,3-diol moiety in 1. Using the anti-3-OVA antibody, a competitive EIA for 1 was developed and evaluated. The range of quantification by the EIA was 0.06-10 ng/mL. The application of the EIA has enabled us to measure the FTY720 concentration in serum after oral administration of 1 (1mg/kg) to rats.
Matsumoto
Norimasa
N
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan. Norimasa.Matsumoto@mitsui-sugar.co.jp
Kohno
Takeyuki
T
Uchida
Shuji
S
Shimizu
Takaaki
T
Kusumoto
Haruko
H
Hirose
Ryoji
R
Yanada
Kazuo
K
Kurio
Wasako
W
Yamaguchi
Shoji
S
Watabe
Kazuhito
K
Fujita
Tetsuro
T
D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000494:pharmacology*; D000937:Antigen-Antibody Reactions; D005260:Female; D000068876:Fingolimod Hydrochloride; D006241:Haptens / Q000737:chemistry; D007124:Immunoenzyme Techniques / Q000379:methods*; D015394:Molecular Structure; D010047:Ovalbumin / Q000737:chemistry; D011409:Propylene Glycols / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011817:Rabbits; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000906:Antibodies; D006241:Haptens; D011409:Propylene Glycols; D010047:Ovalbumin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine