Drug-specific cyclodextrins with emphasis on sugammadex, the neuromuscular blocker rocuronium and perioperative anaphylaxis: implications for drug allergy

• Published in: Clinical and experimental allergy Vol. 41; no. 12; pp. 1663 - 1678
• Main Authors: Baldo, B. A., McDonnell, N. J., Pham, N. H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2011; Blackwell; Wiley Subscription Services, Inc
• Subjects: Allergies; Anaphylaxis; Anaphylaxis - drug therapy; Anaphylaxis - immunology; Androstanols - chemistry; Androstanols - immunology; Anesthesia; Biological and medical sciences; Case reports; Cavities; Cephalosporins; Clinical trials; cyclodextrin; Cyclodextrins - chemistry; Cyclodextrins - immunology; Cyclodextrins - therapeutic use; Drug delivery; Drug Hypersensitivity - drug therapy; Drug Hypersensitivity - immunology; Drug Interactions - immunology; Drug screening; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gamma-Cyclodextrins - chemistry; gamma-Cyclodextrins - immunology; gamma-Cyclodextrins - therapeutic use; Humans; Hypersensitivity; Immunoglobulin E; Neuromuscular Nondepolarizing Agents - chemistry; Neuromuscular Nondepolarizing Agents - immunology; oligosaccharides; Penicillin; Perioperative Period; Pharmaceutical industry; Pharmaceuticals; Drug; Immunopathology; Allergy; Perioperative; Cyclodextrin; Anaphylaxis; Immunology; Sugammadex
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2011.03805.x

Summary Cyclodextrins, oligosaccharides linked in a circular arrangement around a central cavity, are used extensively in the pharmaceutical industry to improve drug delivery. Their usefulness depends on their capacity to form a drug inclusion, or host–guest, complex within the cavity. In an attempt to improve the delivery of the widely used neuromuscular blocking drug (NMBD) rocuronium, a rocuronium inclusion complex was formed with a chemically modified γ‐cyclodextrin. The high binding affinity and specificity of the modified carrier (named sugammadex) for rocuronium (and other aminosteroid NMBDs) led to its use in anaesthesia as an innovative and useful agent for rapid reversal of rocuronium‐induced neuromuscular block by sequestering the drug as an inclusion complex. This, in turn, led to the suggestion that sugammadex might be useful to remove the NMBD from the circulation of patients experiencing rocuronium‐induced anaphylaxis, a suggestion subsequently supported in case reports where traditional treatment had failed. Successful resuscitations suggested that sugammadex might be a valuable new treatment for such intractable cases but, given the inappropriateness of clinical trials, confirmation or refutation will have to await the slow accumulation of results of individual case reports. Important questions related to antibody accessibility of drug allergenic structures on the rocuronium–sugammadex inclusion complex, and the competition between sugammadex and IgE antibodies (both free and cell bound) for rocuronium, also remain and can be investigated in vitro. The sugammadex findings indicate that the use of carrier molecules such as the cyclodextrins to improve drug delivery will sometimes give rise to changed immunologic and allergenic behaviour of some drugs and this will have to be taken into account in preclinical drug safety assessments of drug–carrier complexes. The possibility of encapsulating and removing other allergenic drugs, e.g., penicillins and cephalosporins, in cases of difficult‐to‐reverse anaphylaxis to these drugs is discussed. Cite this as: B. A. Baldo, N. J. McDonnell and N. H. Pham, Clinical & Experimental Allergy, 2011 (41) 1663–1678.