Comparative Study of Pharmacokinetics in the Onset and Offset of Mivacurium and Other Muscle Relaxants

Kim, Sung Yell; Lee, Gin Seung; Hong, Seung Taek; Lee, Jeong Seok; Kim, Soon Im; Kwak, Soo Dal

Abstract

BACKGROUND: The purpose of this study was to evaluate mivacurium in the pharmacokinetics of onset and offset.
METHODS
In 127 adult patients of ASA physical status I or II without any factors involving the neuromuscular function under general anesthesia, onset time (lag and manifest time) and clinical duration were measured after bolus or divided doses of ED95 x 2 of succinylcholine (SCC), rocuronium (ROC), atracurium (ATR), mivacurium (MIV), pancuronium (PAN) or vecuronium (VEC). Recovery time was defined as the recovery index and total duration measured after subsequent ED95 of MIV at 25% recovery of control twitch height from neuromuscular block induced by ED95 x 2 of ATR, MIV, PAN or VEC. Plasma cholinesterase (PChE) levels were measured following PAN or ATR.
RESULTS
Onset time was faster with SCC and ROC, the low potency drugs, than with ATR, MIV, PAN or VEC, the high potent drugs. Manifest time was shorter in low potency drugs but longer in high potency drugs than lag time after bolus or divided doses of muscle relaxants given. Divided doses of various drugs induced a shortened onset time, but the patterns of relationship between lag and manifest time associated with drug potency did not alter. The recovery times with administered MIV were slowest after PAN pretreatment, and fastest after MIV pretreatment. PChE levels decreased significantly from 3 min to over 180 min after PAN administeration but not ATR.
CONCLUSIONS
The onset time of MIV was not improved due to high drug potency as other nondepolarizing neuromuscular blockers. However, in spite of high potency, the recovery time of MIV was faster than other drugs. This results may be depend upon PChE activity rather than drug potency. Additionally, the prolonged recovery of MIV was not only under the influence of low PChE activity but also other some factors such as: the first relaxants administered before MIV dominated the neuromuscular block so that the duration of MIV given subsequently changed to resemble that of the first. The longer elimination half-life of the underlying relaxant prolonged the effects of subsequentshorter acting MIV. Structural similarities or dis-similarities between the interacting MIV and other drugs may have effects more potent in dis-similarity than in similarity.