Cyclodextrins and the emergence of sugammadex

Abstract

Residual paralysis, with its subsequent postoperative pulmonary sequelae, is one of the major complications of anaesthesia, and was recognised shortly after the introduction of neuromuscular blocking drugs into routine clinical practice. Although its incidence decreased with the introduction of intermediate duration drugs, and further diminished with routine neuromuscular monitoring and reversal with cholinesterase inhibitors, residual paralysis still remained a problem. In the search for alternatives to stop the effect of neuromuscular blocking drugs and to match their duration of action to clinical need, chelation of the non-depolarising neuromuscular blocking drugs was considered. It was recognised that cyclodextrins could encapsulate steroidal molecules and thereby inactivate the aminosteroidal neuromuscular blocking drugs. In order to improve the binding of rocuronium to the cyclodextrin and to increase the compound's water solubility, the molecule was modified. This led to the development of sugammadex (Org 25969), a modified gamma-cyclodextrin. The modification of the molecule and the initial in vitro studies that led to in vivo and later human studies of this conceptually new drug for anaesthesia are described.

Comparison of Decurarization Using Sugammadex and Neostigmine After Rocuronium During Desflurane Anesthesia

“…Dosage may change according to the depth of the blockage. A dose of 16 mg kg -1 is applied in the case of intense neuromuscular blockage, 4 mg kg -1 for deep neuromuscular blockage, and 2 mg kg -1 for mild neuromuscular blockage 5,8 . Th e fi rst study on sugammadex administration was performed using a dose of 0.1-8 mg kg -1 following a dose of 0.6 mg kg -1 rocuronium given to 29 healthy volunteer patients.…”

“…It does not interfere with the metabolism of acetylcholine, thus it is not necessary to use anticholinergic drugs concomitantly. Furthermore, it has no proven side eff ects 5,6,8 . Th ey reported; a geometric mean time (95% CI) for recovery of TOF ratio to 0.9 was 1.6 (1.5-1.7) min with sugammadex vs 9.1 (8.0-10.3) min with neostigmine in Chinese subjects.…”

Effects of Intracerebroventricular Sugammadex Administration on Central Nervous System in Rats

“…The cavity size of a, b and c-cyclodextrins are ranged between 4.7-5.3A°, 6.0-6.5A° and 7.5-8.3A° respectively. The size of the cavity diameter determines the molecules that can be encapsulated [11].…”

Anaesthesiology and intensive care The use of sugammadex for the reversal of neuromuscular blockade after thymectomy with videothoracoscopy in myasthenia gravis patients – a preliminary report

“…A correct dose of sugammadex reverses neuromuscular blockade regardless of its depth. Its action does not interfere with the metabolism of acetylcholine; therefore, it does not require the use of anticholinergic drugs, eliminating the risk of their side-effects [8][9][10].…”