PHARMACOKINETICS AND PHARMACODYNAMICS OF MIVACURIUM STEREOISOMERS IN BEAGLE DOGS USING TWITCH HEIGHT AND TRAIN-OF-4 RESPONSE

Mivacurium, a non-depolarizing neuromuscular blocking agent, consists of three isomers; trans-trans (57%), cis-trans (36%) and cis-cis (7%). The purpose of this study was to characterize the pharmacokinetics an d pharmacodynamics of mivacurium after various inputs. Four beagle dog s weighing between 7.95 and 9.89 kg were anesthetized with isofluorane (5%) and received a bolus dose (0.010-0.020 mg kg(-1)) and two consta nt rate infusions (1.0-1.5 mu g kg(-1) min(-1)) of mivacurium via the saphenous vein. Single twitch height (TH) and train-of-four (TOF) were evaluated every 15 and 30 s, respectively. Arterial blood samples wer e collected, processed and analysed for mivacurium using a stereospeci fic HPLC-fluorescence method. The disposition of mivacurium isomers wa s best described by a two compartment model. Mean Cl for the cis-trans , trans-trans and cis-cis isomers were 19.98, 13.53 and 3.47 mL min(-1 ) kg(-1) respectively and the corresponding mean V-dss were 0.29, 0.24 and 1.00 L kg(-1). The measurement of onset showed dose dependence as evidenced by a rapid onset at the higher doses. TOF measurements were more sensitive to the onset of action and required a longer period of time to recover to baseline values as compared with TH measurements. (C) 1998 John Wiley & Sons, Ltd.