The pharmacokinetics and the pharmacokinetic-dynamic relationship of rocuronium bromide

Rocuronium is a new non-depolarising agent with an intermediate time-course of neuromuscular blocking action. In healthy patients its time-course as well as its biodisposition largely resembles that of vecuronium. The initial fast rate of block development may be the result of both low potency amd limited protein binding. The main route of elimination appears to be the hepatobiliary pathway. The time-course of action may be significantly prolonged in patients with severe hepatic disease, mainly because of an increased volume of distribution. A slight prolongation of recovery may occur in patients with renal failure due to reduced clearance. A limited degree of prolongation is observed in the elderly, also largely based on a reduced clearance. In contrast, children below the age of three may show a slower recovery due to a larger distribution volume, whereas in older children the rate of recovery is increased, as a result of an enhanced plasma clearance. Profound hypothermia prolongs the time-course of action by reducimg plasma clearance due to a diminished hepatic uptake. Only limited placental transfer takes place and research evidence suggests that administration of an intubating dose will not produce paralysis or hamper the vital functions of the newborn. Transfer of rocuronium to the cerebrospinal fluid could not be shown in neurosurgical patients. Rocuronium produces a rapid paralysis of the vocal cords due to a combination of an enhanced equilibration rate between plasma and biophase and a low intrinsic potency. Rocuronium is characterised by a context-sensitive half-time between approximately 12-18 minutes following a constant block infusion of 10% twitch height over 30 minutes and over 480 minutes, respectively. This context-sensitive half-time equals the calculated time between stopping the infusion and recovery to 75% twitch height