Pharmacokinetics of the three isomers of mivacurium and pharmacodynamics of the chiral mixture in hepatic cirrhosis.
We have studied the pharmokinetics of cis-trans, trans-trans and cis-cis mivacurium in 10 healthy subjects and 11 patients with mild or moderate hepatic cirrhosis, during nitrous oxide-oxygen-isoflurane anaesthesia. Mivacurium 15 micrograms kg-1 min-1 was infused for 10 min (total dose 0.15 mg kg-1) and the plasma concentration of the three isomers measured at regular intervals for 190 min. The electromyographic response to the drug was also measured. Compartmental analysis of the resulting isomer profiles was undertaken: one- and two-compartment models were fitted to derive clearance, volume of distribution and half-life. Clearance of the cis-trans and trans-trans isomers was reduced significantly in the cirrhotic compared with the healthy group: cis-trans (median (range)) 44 (15-121) ml kg-1 min-1 vs 95 (57-213) ml kg-1 min-1 (P < 0.05); trans-trans 32 (12-64) ml kg-1 min-1 vs 70 (34-101) ml kg-1 min-1 (P < 0.05). The difference in the clearance of the cis-cis isomer in the cirrhotic (4.2 (2.9-12.1) ml kg-1 min-1) compared with the healthy group (5.2 (2.9-8.9) ml kg-1 min-1) was not significant with this sample size. Clearance of each isomer correlated significantly with plasma cholinesterase activity: cis-trans r = 0.73, P < 0.001; trans-trans r = 0.69, P < 0.001; cis-cis r = 0.48, P < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)
Head-Rapson
A G
AG
University Department of Anaesthesia, Royal Liverpool University Hospital.
Devlin
J C
JC
Parker
C J
CJ
Hunter
J M
JM
D000328:Adult; D000768:Anesthesia, General; D002802:Cholinesterases / Q000097:blood; D004576:Electromyography / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000493:pharmacokinetics*; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D003473:Neuromuscular Nondepolarizing Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002802:Cholinesterases