Use of optical biosensor technology to study immunological cross-reactivity between different sulfonamide drugs.
Adverse reactions to medications account for a substantial number of hospitalizations and in some cases fatalities. The nature of the many drug-drug interactions caused by the inhibition of drug-metabolizing enzymes can now be predicted and examined with a greater deal of accuracy due to research developments in the understanding of the drug-metabolizing enzymes. However, the more troubling aspects of drug-drug interactions are the idiosyncratic reactions that are unpredictable and quite often life-threatening. These reactions are often caused by a prior sensitization of a person's immune system to a given drug or class of drugs. The following work offers a technique to examine in a medium-throughput system the cross-reactivity of drugs to antibodies in order to predict if structures share the same antigenic potential toward a sensitized individual. Two commercially important sulfonamide drugs, sulfamethazine and furosemide, were taken and their binding to their respective antibodies were tested in the presence of other structurally related sulfonamide drugs. The BIACORE 3000 biosensor was used for the study and the solution-phase equilibrium assay principle was employed. The data obtained help us determine which drugs can react, and to what extent, with sulfamethazine and furosemide, giving rise to possible allergic or hypersensitivity reactions. Though sulfamethazine and furosemide were used in this study; this principle and methodology can be applied to study any drug molecule-antibody pair.
Ahmad
Ateeq
A
Global Drug Metabolism, Pharmacia Corporation, 4901 Searle Parkway, Skokie, Illinois 60077, USA. aahmad@neophrm.com
Ramakrishnan
Anand
A
McLean
Matthew A
MA
Li
Dongbei
D
Rock
Marie T
MT
Karim
Aziz
A
Breau
Alan P
AP
D015374:Biosensing Techniques / Q000379:methods*; D003429:Cross Reactions / Q000276:immunology*; D005665:Furosemide / Q000737:chemistry / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D055095:Optics and Photonics; D013418:Sulfamethazine / Q000737:chemistry / Q000276:immunology; D013449:Sulfonamides / Q000737:chemistry* / Q000276:immunology*
D007074:Immunoglobulin G; D013449:Sulfonamides; D013418:Sulfamethazine; D005665:Furosemide